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Rohit Sharma might break two Sachin Tendulkar's World Cup records
Indian opener Rohit Sharma is on the verge of breaking two massive Sachin Tendulkar records in the World Cup. He has already broken the 'Most centuries in a World Cup' record by hitting his 5th Century in the match against Sri Lanka in the last league match of both the teams.
Rohit Sharma is in form of his life in the ongoing World Cup
He has been in scintillating form this World cup as he has scored 647 runs in 8 innings. He is only 27 runs shy to break the record of master blaster Sachin Tendulkar of most runs in a World Cup Tournament. Sachin Tendulkar has scored 673 runs in 2003 World Cup in which India reached the finals in the leadership of Sourav Ganguly.
Two records will be on the line for Sharma in the next two games
The Indian opener has hit a total of 6 centuries in World Cup which is equal Sachin Tendulkar's most number of centuries. 5 of them have come in this World Cup breaking the record of Sri Lankan Kumar Sangakkara who had hit four centuries in 2015 World Cup. If Rohit hits one more century he will break the record of great Sachin Tendulkar. If he hits another century he will join Sanath Jayasuriya in the most number of centuries in ODI cricket. The left-hander had hit 27 centuries for Sri Lanka in 445 games.
Read More:- How Australia vs South Africa match affects India
Indian team is well set to take on New Zealand in the 1st Semifinal at the Manchester ground on 9th July at 3 PM IST. India will be high on confidence as they have finished the league stage as the table topper whereas New Zealand has lost their last three matches.
Have a news story, an interesting write-up or simply a suggestion? Write to us at email@example.com

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Greek Chicken Pita Pockets with Homemade Tzatziki
Whew! That title's a mouthful! The sandwich is too. And a very tasty one at that! Perfect for springtime eating!
Tender, extremely flavorful Greek-style chicken with a mixture of crunchy veggies and dollops of cool, creamy cucumbery tzatziiki sauce all in a soft pita pocket. YUM!! Neat? Nope! Not at all! But so, so messily worth it! I've wanted to share this with you for a while now, but can't seem to get any gorgeous photos, but I've decided that it's just too cruel to keep this yummy concoction from you guys any longer. Looks aren't everything, right?!!
First off, let's talk about the greek-style chicken which gets tender and so flavorful by sitting in a nice bath of yogurt, lemon juice and olive oil with a few spices tossed in. The chicken gets ultra tender and has a really nice tang too. And the beauty part of it all is that you bake the chicken in the very same dish you use to marinate it, so cleanup is a snap!
Now, let's talk tzatziki, which is hard to spell and pronounce, but very, very easy to eat! If you're not familiar with it, it's basically a cucumber yogurt sauce that's heavy on the garlic but that zing is balanced out by the cool creaminess of the yogurt. Here it really pulls everything together and is so good, you're going to want to eat it with a spoon! Fortunately, this recipe makes more than you need for just these sandwiches, so you can definitely go the spoon route or use it as a dip for raw veggies or to drizzle on lettuce or other leftover combo bowls (one of my husband's special talents!).
And now, we're on to the pita pockets. When we want pitas, I generally make my own because, hello, I love to bake and once you taste these homemade ones, it's kinda hard to go back to the store-bought variety, but a good quality packaged version will definitely do the trick too, especially when you warm it up.
When everything comes together, there's just the right balance of flavor, color and crunch! Healthy, easy and so tasty! You're going to love these, I promise! They make a great light dinner or extra-special lunch.
Just make sure you've got plenty of napkins handy!!!
Greek Chicken Pita Pockets with Homemade Tzatziki
Makes 5-6 servings
Prep Time for Chicken: At least 2 hours to marinate and up to 12; Bake Time for Chicken: 30 minutes; Prep Time for Tzatziki: 15-20 minutes
For the Chicken
1/2 cup plain, full-fat Greek yogurt (unsweetened)
1/4 cup olive oil
1/4 cup freshly squeezed lemon juice
5 garlic cloves, minced
Kosher salt and black pepper
1 1/2 pounds boneless, skinless chicken breasts
For the Tzatziki
2 cups (554 grams) plain Greek yogurt (unsweetened)
1 English or seedless cucumber, unpeeled
2 tablespoons freshly squeezed lemon juice
1 tablespoon white wine vinegar
2 medium cloves garlic, minced
1 1/2 teaspoons kosher salt
1/2 teaspoon freshly ground black pepper
For the sandwiches
Fresh pita pockets, store-bought or this homemade version
Shredded lettuce
Fresh tomatoes, sliced
1 cucumber, sliced
The Recipe
1. To make the chicken: Mix together the yogurt, oil, lemon juice, garlic and a pinch or two of salt and pepper together in a 9x13-inch baking dish. Add the chicken and coat it with the yogurt mixture. Cover and let marinate in the fridge for at least 2 hours and up to 12.
2. When you're ready to cook the chicken, remove it from the fridge so it can warm up a bit and preheat oven to 425ºF. Bake the chicken for about 30 minutes, or until cooked through and browned on top. Let cool for about 10 minutes (or more) and slice thinly.
3. To make the tzatziki: While the chicken is marinating or even the day before, place the yogurt in a medium bowl. Cut your cucumber lengthwise and quarter it. Then scoop out the seeded part. Coarsely grate your cucumber onto a clean dishcloth and wring it out as well as you can over the sink. You really want to get as much liquid out as possible or the sauce will be too runny. Add the grated cucumber to the yogurt, as well as the lemon, vinegar, garlic, salt and pepper and stir to combine. Taste and add more salt and pepper if needed. Chill covered, until needed. You can definitely make this a day ahead and keep covered in the fridge.
4. To assemble the sandwiches: Warm the pitas and then cut open and stuff with shredded lettuce, chicken, tomatoes and cucumbers and top with dollops of the tzatziki sauce. Serve immediately.
Note: Chicken recipe adapted from The Half-Baked Harvest Cookbook. I cut the smoked paprika and oregano. Tzatziki recipe adapted from various versions online and in cookbooks. I'm not a huge dill fan but if you like it, it would be nice to add some freshly chopped dill to it as well.


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I'm a girl who lives in London (no where near Big Ben though). I'd say that it is always cold here which annoys me. I'm part Moroccan by my dad (who sadly died 23/06/10 I miss him loads) and Oujda is the town he grew up in (My name has nothing to do with Ouija boards). I'm also part Irish (by my mum- being mixed is awesome). I probably use the word awesome a bit too much and have the tendency to be too quiet in class and then too loud every where else. I love to read and after starting a children's novel all the way back on 25/01/10, I've finally finished it. With a word count of around 85k and way too many mistakes; I'm at the editing stage. Thankfully, my best friend (Duckies-on-a-Trampoline) is going to proof-read it as well as my own efforts. And then comes the hardest part of all: trying to get it published! (Anyone want to tell me good luck?) I play the violin but, personally, I think I fail at it and that a dying cat sounds better, but that's just my opinion. I am Team Edward, but also many other teams. Twilight seems to be the only story that everyone knows about and because I know quite a lot about it; people assume I'm obsessed. I love the fandom though I'm absolutely mad, according to anyone that really knows me but don't worry, they're all the same. LAst of all: My fanfiction name is Oujdagirl. :)
Everything from Push-ups to Daisy Chains can invoke a kiss. And how strong is Edward?
Light, Fluff and Fun. Bella X Edward. Post-Twilight. One-shot.
(Nothing to do with Pushing-up daisies) Enjoy!
All publicly recognizable characters, settings, etc. are the intellectual property of their respective owners. The original characters and plot are the property of Stephenie Meyer. No copyright infringement is intended.


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Whether you work in a home office or abroad, business success in our ever more globalized and virtual world requires the skills to navigate through cultural differences and decode cultures foreign to your own. Renowned expert Erin Meyer is your guide through this subtle, sometimes treacherous terrain where people from starkly different backgrounds are expected to work harmoniously together. When you have Americans who precede anything negative with three nice comments; French, Dutch, Israelis, and Germans who get straight to the point ("your presentation was simply awful"); Latin Americans and Asians who are steeped in hierarchy; Scandinavians who think the best boss is just one of the crowd--the result can be, well, sometimes interesting, even funny, but often disastrous. Even with English as a global language, it's easy to fall into cultural traps that endanger careers and sink deals when, say, a Brazilian manager tries to fathom how his Chinese suppliers really get things done, or an American team leader tries to get a handle on the intra-team dynamics between his Russian and Indian team members.
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Come 27th September, Uganda will be celebrating the World Tourism Day. This year's celebrations are aimed at increasing individual awareness of the great role of the tourism industry across the entire international community as well as how it has affected the economic, cultural as well as social situations across the globe.
We as AA Safaris & Tours Ltd are supporters of sustainable travel of the Tourism industry in Uganda, and have at all times been very mindful to the substantial potential of our tourism sector for the benefit if the local people. Because this sector is among the largest financial contributors in most countries across the globe, it can as well assist transform the economies of several poor countries. Nevertheless, in developing countries, emerging reports indicate that for each $100 dollars that every tourist spends, $5 stays are retained by the economy of the host country where the tourist activities are being enjoyed.
Ever since the beginning of AA Safaris & Tours Ltd, we have been in engaged in primarily these types of travel which as much as possible profit the natives. We as a company have always advocated eating in the local restaurants as well as making our reservations with accommodation facilities that are locally owned. We also believe that improve tourism will certainly make the entire world a much better place through interacting with neighbors living on the other side of the planet, learning about their ways of life and survival, and promoting inter-cultural interaction. This kind of tourism also offers an opportunity to learn, respect as well as recognize other foreign cultures in manners that assist preserve and uphold the native identity. With the achievement of sustainable tourism, we shall be in position to offer back to several communities as well as the entire alliance will be for all.
As part of the Uganda Safari Packages we offer our clients are a number of community trips specially enjoyed during our Uganda Cultural Safaris. We also organize exciting cultural tours in Rwanda which include day trips or overnight tours. Among the most outstanding communities in which we conduct our trips include: the Karimojong people living in the remote Morungole Mountains of Kidepo National Park, the Batwa pygmies living in Mgahinga and Bwindi National Park, the Bigodi Community living close to Kibale National Park, the Banyankole people living at the edge of Lake Mburo National Park, the Boomu Women community living within Murchison Falls National Park, the Bambuti living in Ntandi within Semuliki park, the Ruboni Community inhabiting the foothills of Mt. Rwenzori (mountains of the moon) as well as a number of Island communities living on Lake Bunyonyi.
The republic of Uganda will be joining the rest of the globe to celebrate the international tourism day. There will be various celebrations to mark this day here in Uganda and these will include tourism exhibitions, cultural performances as well as colorful vibrant matching. This day has turned into a tourism flag-event for Uganda since it is currently being used to market Uganda Safari Packages on the international scene. The theme for the 2016 World Tourism Day is 'Tourism for all' in accordance with the aim of increasing awareness of the benefits of tourism among the local people.
For more information about Safaris in Uganda, please visit ugandasafariguide.com


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Beloved swan at Canton vineyard dies after being hit by car
CANTON, Ohio– Gervasi Vineyard in Canton is mourning the loss of one its beloved swans.
Guiseppe was hit by a car and killed while trying to cross 55th Street NE to the pond at Rice's Nursery. His body was found Sunday morning.
The vineyard said Guiseppe and his partner, Gina, look for nesting sites each spring and that involves crossing the busy street.
"Since Swans mate for life, we are very concerned for Gina's well being," Gervasi Vineyard said on Facebook.
Anyone with information on a male swan that needs a home should contact the vineyard.
40.857273 -81.351396


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The Government is proposing major reforms to the prison system in England and Wales. Giving governors more discretion over the use of Release on Temporary Licence (ROTL) is likely to be amongst them. This Briefing Paper focuses mainly on England and Wales, but it also briefly considers the schemes which operate in Scotland and Northern Ireland.Jump to full report >>
ROTL allows offenders to be released temporarily into the community for specific purposes, such as to engage in employment or to receive medical treatment.
According to Government guidance, the main purposes are:
The policy became particularly controversial in May 2014 when a violent armed robber, Michael Wheatley, absconded whilst on temporary licence from an open prison. Before that, in the summer of 2013, there were three serious incidents where prisoners released on temporary licence committed offences. These led to a review by Her Majesty's Inspectorate of Prisons.
In response to these serious incidents, in March 2014 the then Justice Secretary Chris Grayling announced that the rules would be tightened up. The changes included:
Interim guidance followed, and the current guidance, Prison Service Instruction 13/2015, Release on Temporary Licence was published in March 2015.
Not every prisoner can be released on temporary licence. Some, such as those categorised as posing the highest security risk, are barred altogether. Others, such as those with a history of absconding, would only be eligible in exceptional circumstances.
Since a peak of just over 529,000 incidences in 2013, the use of ROTL has fallen considerably. In 2015, there were just over 333,000 incidences of prisoners being released on temporary licence. This is the lowest number of incidences since 2003:
Data for 2010 is unavaible due to a new prison database system being introduced in mid 2009 (P-NOMIS)
There were 162 "temporary release failures" in 2015. "Failures" cover absconding and late return, alleged offending whilst on licence and other breaches of the licence conditions. There were 49 failures per 100,000 incidences of ROTL in 2015; the annual number of failures per 100,000 incidences has more than halved since 2002.
In May 2016 the Justice Secretary Michael Gove said he wanted to "rethink ROTL". He pointed to its advantages in rehabilitating prisoners, and announced plans to give prison governors much more control over this and other aspects of prison management.
Commons Briefing papers SN06878
Authors: Pat Strickland; Grahame Allen
Topic: Prisons
The House of Commons Library provides research, analysis and information services for MPs and their staff.


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The Key to the Way the World Works
Henry Young, Sep 1, 2007 - Religion - 52 pages
Inside of your head is a method that you use to prove something to yourself. It discriminates against or for the things seen, heard or sensed as if to protect an interest. Our world represents a culmination of the interplay of both internal and external opposing energies from all in existence. They are represented on a sliding scale from the most influential to the most subtle. This interplay is recorded in our memory. What if you could take it out of your head and examine it. What would it look like? How would it work? If you had this information, you could use it to heal yourself and others. You could also prove a point, improve the world or use it as a research tool.
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I watched about 4 disney movies and a couple sings-a-longs today with my mom's boyfriend's kids....tons of fun. I didn't get to walk down to the beach today, because they were here but oh well, I will do it tomorrow.
I was thinking about how it is funny, that you can read people's livejournals but never talk to them in person...hah, oh well.
Last night was fun...I got to hang out with people and the bands were good. AND I got to see vern! I was sooooo happy.
hmm... I am going to go watch a movie...CHOW
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Monoprice Select Mini Bed Level Calibration Testby elfworks May 5, 2017
Please Login to Comment
This is a great print! Thank you for such a simple and easy to use test! With a simple pair of calipers, you're able to measure the height differences between all four corners, and the center.
Thank you for coming up with, and designing such a great test!
The screws holding the bed of the Monoprice Mini have a thread pitch of 1mm.
(Based on my measurements. Please correct me if I'm wrong.)
On my V1, they are metric M3 screws with a standard pitch of 0.5 mm.
Yeah, I think you're correct.
I've updated the notes.
Used another print to get my bed height right, and then realized that it wasn't level. This was the perfect print to get it leveled out again. Thanks!
Can someone explain how to use this? I'm not quite sure how it works, but I know I need it :)
I use it to fine tune my bed height.
You have to use the print settings listed in the description.
Print it out and watch the first layer go down.
As it prints the first layer, you can tell if any of the corners are at the wrong height.
If the corner is too high, the extruded filament looks too flat, and adjacent passes squish together. (Turn that corner screw clockwise a bit to lower the bed.)
If the corner is too low, the extruded filament looks too round, and adjacent passes don't properly fuse together. (Turn that corner screw counter-clockwise a bit to raise the bed.)
If the bed is at the right height, the first layer should be firmly adhered to the bed, and the adjacent passes should be fused together, with just the slightest bit of rounding on top. (Here's a good example I found by Googling '3d printer proper bed height': https://i.stack.imgur.com/AbVDV.png )
I usually tweak the screws while the print is going, and just keep re-printing the first layer until I'm happy with the settings.
Finally, if you let it finish printing, you can use calipers to verify that it's printing correctly on all axes. The different layers are calibrated at .5mm, 1mm, & 5mm, the squares are 10mm x 10mm & the outer square is 100mm x 100mm. The wall thickness is .8mm.
I've noticed that when loaded into cura, the corner squares don't touch the bed. is that intentional? The bottom of the entire model is marked in red.
Not intentional. :)
This was one of my early models, and it's just a bunch of overlapping objects.
Cura marks it in red, but if you switch the view mode to Layers, you'll see it slices properly.
Ah, I see. I've printed it a number of times, but i've had to mess with settings to get the corner squares to actually print properly because they sit off the bed.
If you slice it using the supplied settings, you shouldn't have any adhesion issues.
Look at the Layers view in Cura.
If your corners aren't sticking, you have bed adhesion/height issues.
It's not about them not sticking, its that there wasn't any paths on the bottom layer for the outside edges of the corner squares. see: https://imgur.com/rN3nMA3
That's weird?!?
I'm using Cura 2.7.0.
Is wall thickness set to .8mm?
It would seem enabling cura's "union overlapping volumes" "fixes" the problem.
Thanks for following up with a solution to the problem!
I was able to replicate your problem. (I had enabled that option many moons ago, and forgot that it wasn't on by default.)
I knew the model was a mess, but it always sliced correctly for me. You're the first to mention the error.
I have rebuilt the model so it slices properly, and saved it in STL format. (Even got the preview to show up correctly.)
Thanks again for helping me fix this problem.
Not a problem at all :) it confused the crap out of me a while back, and I only just loaded it up a gain and saw it, and had to re-figure out the issue.
Excellent for calibrating the base height. I ran the print and played with the screws while it printed to get a good height. I noticed immediate results with my next print. As noted, you only need to print the first layer for plate calibration.
Thanks elfworks!


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My movie "Lagos Real Fake Life" will receive first Nigerian Oscar award – Mike Ezuruonye
Popular filmmaker Mike Ezuruonye, says that cinematography and story telling of Nigerian movies has vastly improved over the years and could earn international recognition in due course.
Ezuruonye told the NAN on the sideline of the private screening of his upcoming movie, titled "Lagos Real Fake Life", at the Palms Mall, Lekki, Lagos that Nollywood movies could be nominated for an Oscar prize in the nearest future.
"Everything about Nollywood movies has vastly improved over the years and the movies that come out have great cinematography, editing and ticks all the right boxes.
"Nollywood movies have stuck to its originality while still improving in other ways and we are the best in Africa in terms of everything that concerns movie production.
"The Academy Awards, which is also known as the Oscar, is an award that every actor wants to get because it takes you to a whole different level and I'm pretty sure that our movies would soon be nominated for it.
"Hopefully, my movies would be first to win an Oscar award and help in putting Nollywood on the global map," he said.
Ezuruonye, who also the directed "Lagos Real Fake Life", said that the movie would help in addressing the pressures of living fake lifestyles which was common among youths.
"The movie would help in addressing the societal pressure of living fake lifestyles amongst youths and correct that notion.
"People must understand that living fake lifestyles are really expensive to maintain than a real one so we must always strive to be ourselves in all ramifications.
"The movie would expose the mistakes most youths are fond of making and help the people to understand that fake grass is greener than the real ones," he said.
The movie is based on two main characters, Mike Ezuruonye and Nonso Diobi who play Chidi and Emeka who living fake lifestyles to deceive people for their selfish gain.
The array of A-list actors in the movie includes Odunlade Adebola, Mong Kalu, Mercy Aigbe, Ik Ogbonna, Annie Idibia and Nedu Wazobia.
Others are Emmanuella, Rex Nosa, Hadiza Gabon, Uzee Usman, Nikky Ufondu, Josh 2 Funny, Mr Jollof and Haillie Sumney.
Lagos Real Fake Life will be released in cinemas on Nov. 16.
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13 Nursing Homes near Manassas, VA
There are 13 Nursing Homes in the Manassas area, with 3 in Manassas and 10 nearby.
To help you with your search, browse the 80 reviews below for nursing homes in Manassas. On average, consumers rate nursing homes in Manassas 2.7 out of 5 stars. Better rated regions include Fairfax with an average rating of 3.3 out of 5 stars.
Caring.com has helped thousands of families find high-quality senior care. To speak with one of our Family Advisors about nursing home options and costs in Manassas, call (855) 863-8283.
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District Home at Birmingham Green
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Manassas Health And Rehab Center
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Fairfax Nursing Center
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Nursing Homes near Manassas, VA
Other Options in Manassas, VA
Recent Reviews of Nursing Homes in Manassas
Review of Manassas Health And Rehab Center
We transferred my Dad from a skilled nursing facility in Bozeman, Montana to Lake Manasssas Rehab. His Doctor in Montana had refused to eliminate some of his meds and I knew that the only way to gi... Read more
Review of District Home at Birmingham Green
Birmingham Green was a very nice facility. I was pleasantly surprised when I went there. The staff was very friendly and even the residents seemed more lively, which was a vast improvement over som... Read more
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Emily Atack weight loss: How much weight has Emily Atack lost during I'm a Celebrity 2018?
EMILY Atack was runner-up in this year's I'm A Celebrity Get Me Out Of Here. But how much weight did Emily Atack lose in the jungle?
Emily Atack showed off her half-stone weight loss as she posed for the cameras at the Versace hotel in Brisbane after leaving the jungle on Sunday. The Inbetweeners actress also had hundreds of painful looking insect bites on her arms and legs as she talked about her experience on the hit ITV show. She finished in second place after football manager Harry Redknapp was crowned King of the Jungle during the final of the show on Sunday night.
The 71-year-old also lost an impressive stone in weight after the campmates survived on a diet of rice and beans for three weeks.
Emily's manager and younger sister Martha also praised her sibling for promoting a healthy body image on TV by showing off her size ten physique.
She said to The Sun: "Emily has 100 per cent embraced her curves.
"She's never been a diet or gym obsessed girl but she's always been conscious of being 'curvy' as actresses are so often tiny.
Emily Atack weight loss: The actress came second in this year's I'm a Celebrity
"She used to tell me she would be the biggest girl at a casting and she was only a size ten.
"I think going through her twenties she's totally embracing herself more. I think the jungle has done that."
Who is Emily Atack?
The 28-year-old was born on December 18, 1989 in Luton and is the oldest child of actress and singer Kate Robbins, who is also a first cousin once removed of Beatles rocker Paul McCartney.
She is most known for her role as Charlotte Hinchcliffe in the E4 series The Inbetweeners.
Emily has also appeared in films such as the remake of Dad's Army and television shows including Rock and Chips.
She was also voted off in the eighth week of Dancing On Ice in 2010.
The comedy actress hit the headlines earlier in the year after being romantically linked to comedian Seann Walsh.
Rumours surfaced that Emily "clicked" with comedian Seann Walsh at the Edinburgh Fringe Festival two years ago.
Seann was dating actress Rebecca Humphries at the time, who he recently split up with following his kiss with married Strictly Come Dancing partner Katya Jones.
But Emily has kept tight-lipped about the speculation and refused to talk about Seann.
She told OK! magazine: "I think Seann has had enough stuff in the press about him, so I won't be talking about Seann.
"When you start talking about your love life in the public life it's a recipe for disaster."


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The Treatment and Management of Type 1 Diabetes Mellitus: 2019 Update
Sheryl Merkin, M.S., F.N.P., C.D.E., Sharon Movsas, M.S., R.D., C.D.E. and Joel Zonszein, M.D., C.D.E.
Dr. Zonszein is Professor of Clinical Medicine, Albert Einstein College of Medicine. All authors are staff members of the Clinical Diabetes Center of Montefiore Medical Center, New York.
Updated by Kristen Welch, M.D., Ben Alencherry, M.D., and Nadine El Asmar, M.D.
Drs. Welch and Alencherry are Internal Medicine Chief Resident Physicians, and Dr. El Asmar is Assistant Professor, Department of Medicine, University Hospitals Cleveland Medical Center and Case Western Reserve University and Louis Stokes Cleveland VA Medical Center.
Within the past 12 months, Drs. Alencherry, El Asmar and Welch report no commercial conflicts of interest. Albert Einstein College of Medicine, CCME staff and interMDnet staff have nothing to disclose relevant to this activity.
Release Date: 06/11/2019
Termination Date: 06/10/2022
Estimated time to complete: 1 hour(s).
Albert Einstein College of Medicine designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Albert Einstein College of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
Learning ObjectivesUpon completion of this Cyberounds®, you should be able to:
The correct answer is: "None of the above."
Metformin, an oral agent that decreases hepatic glucose production, has no indication in the treatment of Type 1 diabetes.
Nateglinide, an oral agent that causes insulin secretion, has no indication in the treatment of Type 1 diabetes.
Pioglitazone, an oral agent that causes insulin sensitivity, has no clear role or indication in the management of individuals with Type 1 diabetes.
The patient has improved insulin secretion and better glycemic control as a result of insulin therapy and resolution of glucose toxicity. This window of improvement in glycemic control is also known as the "honeymoon period of the disease," tends to vary in time, but is often associated with mild hyperglycemia that can cause chronic complications(1)(2)(3)(4)(9) and less islet β-cell function later in the course of the disease.(6) Delaying intensive insulin treatment, therefore, will be conterproductive in these patients. This strategy needs to be explained as part of the necessary education for individuals with Type 1 diabetes, i.e., intensive insulin therapy is recommended.
After the Diabetes Control and Complications Trial (DCCT) findings showed that improved glycemic control with intensive insulin therapy in patients with Type 1 diabetes mellitus led to significant reductions in retinopathy, nephropathy, neuropathy particularly and microvascular complications to a lesser extent,(1)(2) achieving glycemic control as close to normal (A1C 6-7%) without meaningful hypoglycemia has become the standard of care.
Insulin Overview
Insulin administration is meant to mimic the body's natural insulin production to achieve certain glycated hemoglobin (HbA1C) and blood glucose targets. Typical regimens have usually been done in a basal/bolus method with long or intermediate insulins given as basal dosing and pre-meal regular or short-acting insulin as the boluses. These insulin formulations can be injected separately or mixed in the same syringe. Rapid-acting insulins are available as analogues which include insulin lispro, insulin aspart, insulin glulisine and a non-injectable rapid acting inhaled insulin, (Afrezza®), though use of the latter has been limited. These insulins better mimic naturally-secreted meal insulin bursts when compared to regular insulin. Long-acting insulins are also available as analogues. These include glargine, detemir and degludec which have quickly replaced the intermediate-acting insulins such as lente and NPH, and the long-acting insulin, ultralente.(10) The long-acting insulin analogues are more predictable with less variability in glycemic changes. Table 1 includes a complete list of all types by category.
Table 1. New and Commonly Used Insulins: Basal and Bolus.
Current available types of insulins with corresponding peak onset and duration listed in hours. Brand names listed in parentheses. Modalities other than intermittent subcutaneous injection in brackets.
Conventional insulin therapy regimens use a single daily injection, or two injections per day (regular and NPH insulin, mixed together in the same syringe, given in fixed amounts before breakfast and dinner). This is now replaced with insulin regimens providing a basal bolus approach. The stable basal insulin is given as one to two daily injections of intermediate- or long-acting insulin, or via continuous subcutaneous insulin infusion (insulin pump). Bolus insulin — regular insulin, rapid-acting insulin analogues or the rapid-action inhaled insulin — is given in addition to the basal insulin before each meal. It is worth mentioning that available inhaled insulin formulations have fallen out of favor due to problems with absorption, increased hypoglycemia and increased respiratory adverse effects.(36) The choice of regimen and type of insulin is individualized and depends on each patient's lifestyle and preference.(12) For optimal insulin regimens, understanding insulin pharmacokinetics is critical, as the duration of action is affected by such factors as the type of insulin preparation, insulin dose, injection technique and site of injection.(13)
Patient education about insulin addresses a few basic issues — unused vials should be refrigerated and both extreme temperatures and excess agitation avoided — to preserve its potency. When clumping, frosting or precipitation are noticed, the insulin should be replaced. An extra bottle of each type of insulin used should always be available.
Conventional insulin administration involves injection with syringes that are now available as 0.3 cc (up to 30 units), 0.5 cc (up to 50 units), and 1 cc (up to 100 units) with smaller (30 and 31 gauge) needles of several lengths. Prescriptions should specify the type of syringe and needle. When pen syringes are used instead of the classical syringes, prescriptions for the pen syringe, as well as the pen needles, also need to be specific. Insulin syringes and pens, needles and lancets should be disposed properly either through needle disposal programs or placed in a puncture-resistant container; local trash authorities should be contacted for proper disposal and to assure that these containers will not be recycled.
Figure 1. Insulin Pens.
Basal Insulins: Intermediate and Long-Acting
Exogenous basal insulin is provided continuously throughout the day with the goal of normalizing non-meal related blood sugars. Although it is meant to resemble the sustained non-meal related endogenous insulin, a true physiologic replication is extremely difficult. Also, insulin is administered peripherally and not via the portal system that is the case with endogenous insulin that is constantly changing in response to the provision of fuels and the regulation of many other hormones. Thus exogenous insulin with fixed absorption rates and duration of action cannot replicate the intricate endogenous insulin secretion.
Until recently, NPH has been the classic basal insulin, used widely in DCCT.(2) In Type 1 diabetes, NPH insulin should be given as two injections — in the morning and at bedtime. The bedtime dose attempts to take advantage of its peak — the maximum insulin oncentration/effect that occurs six to seven hours later — to meet the increased insulin demands that take place in the morning (dawn phenomenon). When given before dinner NPH may cause hypoglycemia as it typically peaks around 3:00AM, the same time of the physiologic glucose nadir. In practice, however, NPH peaks are difficult to predict because of high intrapatient and interpatient variability. Thus, the long-acting insulin analogues (glargine, degludec and detemir) provide more steady basal replacement, resulting in less hypoglycemia and less hyperglycemia. Though they offer better control, they still do not replicate physiologic secretion of basal endogenous insulin production. Another advantage of the long-acting insulin analogues is improved absorption leading to less intra-patient variability, allowing for more predictability. (14)
Insulin glargine, introduced in 2001, was the first insulin analogue with a prolonged duration of action to become available. (15) Insulin glargine differs from human insulin in that the amino acid asparagine at position A21 is replaced by glycine and two arginines are added to the C-terminus of the β-chain. These amino acid changes reduce the aqueous solubility of insulin glargine at physiologic pH, stabilizing the hexamers and delaying its dissociation into monomers. It is released gradually from the injection site with a slow absorption which results in a relatively constant basal insulin supply. Glargine is formulated as a clear acidic solution and because of its low pH cannot be mixed with other insulins.(16) Therefore, a basal/bolus regimen using glargine requires four injections a day compared to a basal/bolus regimen using NPH which requires three injections a day. Glargine comes in U-100 and U-300 formulations. U-300 glargine is newer and delivers the same number of units in a smaller volume. The smaller insulin depot reduces the surface area leading to a slower release of insulin overtime, which results in a longer duration and a more predictable pharmacologic profile. (14)
While NPH insulin has a peak action at six to seven hours after injection, with detectable serum insulin concentration levels after 17 hours, insulin glargine only has a small peak at four hours and remains active at 24 hours. Studies comparing NPH twice-daily plus two pre-meal boluses at breakfast and dinner to glargine once-daily plus three pre-meal boluses have shown that the glargine regimen has fewer hypoglycemic episodes, particularly nocturnal hypoglycemia, lower fasting blood glucose concentrations and produces the same or slightly improved A1C values.(17)(18) While many patients achieve stable basal serum insulin concentrations with a single daily injection of glargine, given in the morning or evening (it is approved to be given at any time of the day), some patients with Type 1 diabetes may need twice-daily insulin injections.
Insulin detemir, approved by the FDA in June 2005, was the second long-acting insulin analogue.(19) The prolonged action of this insulin is attributable to the addition of a fatty acid side chain that allows a constant albumin binding and unbinding which results in a steady insulin serum concentration and less variability of blood glucose concentration. The duration of action is dose-dependent but appears to be shorter than that of insulin glargine. Insulin detemir, brand name Levemir®, has been approved by the FDA to be used once or twice daily in patients with Type 2 or Type 1 diabetes. Glycemic control appears to be superior with detemir in trials comparing twice daily insulin detemir and NPH.(20) Additionallly, insulin detemir is associated with less nocturnal hypoglycemia, better fasting blood sugars and less weight gain.(21)(22)(23)
Insulin degludec is an ultra-long acting insulin analogue approved by the FDA in 2015. It has a deletion of the threonine amino acid residue at B30 and the addition of a fatty acid to lysine at B29, and is formulated with zinc.(14) The drug self-aggregates and forms stable multi-hexamers. Diffusion of zinc from these results in a slow absorption of the insulin, leading to stable and continuous delivery.(24) Analyses have shown that the effect is evenly distributed across the entire half-life of the drug (25 hours), with decreased intra-patient, day-to-day variability of its glucose-lowering properties.(24) Studies from the BEGIN clinical trial program investigating degludec, found significant reductions in mean daily basal, bolus, and total insulin required with degludec compared to glargine- with the implication that if switching a patient from glargine to degludec doses may need to be reduced. (24) No significant differences in rates of overall hypoglycemic episodes were found in the BEGIN trials focusing on degludec vs glargine in Type 1 diabetics.(24) Given its longer half-life and stable delivery, degludec also allows for flexibility of timing once daily doses to adjust to different lifestyles without large fluctuations of insulin in circulation that may be seen in other basal insulins.
The correct answer is: "Start a basal-bolus insulin regimen."
Although the patient's glycemic control improved significantly and he was doing fine with basal insulin only, evidence based medicine supports a more aggressive approach in order to reduce the risk of diabetic retinopathy, nephropathy, neuropathy(2)(3)(6)(7)(8) and macrovascular complications.(1) Intensive therapy markedly reduces the risk of progressive retinopathy and is more effective when introduced during the first five years.(2) The mechanisms by which early intensive insulin management prevents long-term complications known as the "metabolic memory" are unclear;(9) any elevation in glycemia, even in the subdiabetic range, can increase the risk for cardiovascular disease.(11) Thus, implementation of intensive insulin therapy as early as possible and maintenance of good glycemic control as long as possible result in a short- and long-term reduction of complications. Also early intensive insulin treatment results in better metabolic control short and long term, probably by preserving beta cell function.(13)
Changing from glargine to detemir at bedtime will not improve glycemic control. Detemir works for 12 hours, thus two injections are often required. The advantages of switching to detemir are less hypoglycemia, less weight gain and improvement in fasting blood glucose, none of which was an issue at this time in this case.
Changing from glargine to two injections of detemir will not improve glycemic control. While advantages of switching to Levemir are less hypoglycemia, less weight gain and improvement in fasting blood glucose, none of which was an issue at this time in this case.
Glargine, a basal insulin, cannot prevent postprandial glycemic surges in insulinopenic individuals. Sooner or later, the patient will need to add pre-meal bolus injections. There is plenty of evidence that earlier and more aggressive treatment will result in fewer complications and better glycemic control.(1)(2)(3)(6)(7)(8)(9)(11)
This patient already has an effective basal regimen. Switching to two injections of NPH will cause more glucose variability, because of the NPH peaks, so that a bolus regimen will still be necessary.
A more intensive insulin regimen is necessary not only to avoid chronic diabetic complications but also for preservation of beta cell function and easier management.(13) Since the patient has adequate basal insulin, bolus insulin will improve postprandial glycemias. Bolus insulin doses change constantly and need to be calculated by the patient according to the blood sugar level (correction factor), carbohydrate to insulin ratio (CIR) related to insulin sensitivity and carbohydrate content of each meal. Since education for self-insulin adjustments takes some time, he was initially prescribed a fixed dose.
Bolus Insulins: Rapid-acting Analogs, Regular and Inhaled
In addition to regular insulins, there are three rapid-acting injectable insulins and one inhaled insulin that can be used for pre-meal boluses. Rapid-acting insulin is designed to have a faster onset and shorter duration than regular insulin. Modifications made to the insulin molecule, by substituting an amino acid(s) in the β-insulin chain, permit faster absorption, quicker peak action and shorter duration (see Table 1).
Compared to regular insulin, rapid-acting insulins allow easier timing with meals, achieve better reductions in postprandial hyperglycemia and provoke fewer instances of hypoglycemia.(25) But they also may result in hypoinsulinemia and hyperglycemia five to seven hours after injection due to their shorter duration of action.(26) When this occurs, it is necessary to increase the dose of the intermediate or long-acting insulin.
Rapid-acting insulins allow easier timing with meals.
Rapid-acting insulins are more convenient for patients using intensive insulin therapy, as they correct hyperglycemia more rapidly than regular insulin. These effects appear to be equally effective in the three analogues.(27)(28)(29) Results from clinical trials show only small differences in the reduction of A1C between the analogues and regular insulin.(30) Rapid-acting insulins cost more, and the possibility of teratogenicity and long-term safety are unknown. Ideally, rapid acting insulins are given around 10-20 minutes before a meal, since giving it before (as opposed to during) has been shown to reduce post-prandial glucose spikes more. (14)
Insulin lispro was the first commercially available analogue. Lispro is identical to human insulin except for a reversal of the B28th and B29th amino acid residues (proline and lispro, respectively), permitting it to act similarly to monomeric human insulin. Lispro has the pharmacokinetic profile of the rapid acting insulins and thus better mimics the normal prandial insulin surge in response to carbohydrate ingestion.(31)
Insulin aspart was the second rapid-acting analogue, engineered through replacement of the proline residue at position 28 of the β-chain with aspartic acid. The replacement decreases self-association of insulin aspart monomers, resulting in a pharmacokinetic profile similar to lispro's, and it is, thus, well suited for use as meal insulin.
Insulin glulisine was FDA approved in April 2004.(32) This rapid-acting insulin analog differs from human insulin by the replacement of the amino acid asparagine with lysine at position 3 and lysine with glutamic acid at position 29 of the β-chain. Compared with regular insulin, and similar to other rapid analogues, glulisine has a more rapid onset of action and a shorter duration of action.(33)
Inhaled insulins present an attractive option for bolus insulin in patients with diabetes. They were first introduced into the U.S. market in 2006 with Exubera, but Exubera was discontinued the next year after poor sales.(34) Afrezza (human insulin) was approved by the FDA in 2014.(35) Inhaled insulin may be used in diabetic adults who do not smoke or have any lung disease. Their use has fallen out of favor due to numerous concerns with administration, delivery, hypoglycemia and adverse pulmonary effects.(36)
The use of inhaled insulins has fallen out of favor due to numerous concerns.
Figure 2. Insulin Inhaled Device (Afrezza)
The Afrezza inhaler device on the left with its different insulin cartridges on the right with their corresponding units of insulin. (37)
Fixed combinations insulins are commercially prepared mixtures where the basal and bolus insulins are divided with the intention (unsuccessful) of replicating physiological insulin production.(14) However, they do serve a purpose, especially initially in patients who require a simpler and more convenient method of physiologic insulin replacement, but glycemic control is often hard to achieve because they limit optimal individualized basal-bolus needs.(5) Novolog 70/30, for example, is a fixed combination (70% of protamin aspart suspension and 30% soluble aspart insulin; all recombinant DNA human insulin) that is given twice daily before breakfast and dinner at a prescribed dose without self-adjustment. The protamine component of the aspart and lispro premixed insulins functions like NPH.(15) While simpler to implement, this type of regimen is associated with long-term weight gain and hypoglycemia, both of which often lead to compromised adherence. As the name suggests, "fixed combinations" limit individualization and flexibility; raising basal insulin requires raising the bolus insulin and vice versa. Insulin dosage adjustments based on basal needs can impose a dietary modification to offset the increase in bolus insulin. Hence, patient education on consistency of meal timing and carbohydrate content is indicated.
Insulin preparations with a predetermined proportion of intermediate-acting insulin mixed with short- or rapid-acting insulin (e.g., 70 percent NPH/30 percent regular, 50 percent NPH/50 percent regular and 75 percent NPL (protaminized insulin lispro)/25 percent insulin lispro) are also available and are shown in Table 2.
Table 2. Fixed-Mixed Insulins.
The percentage of rapid or very rapid insulin is shown as the denominator.
Pramlintide Acetate
Pramlintide acetate (Symlin®) is a synthetic analogue of human amylin, an islet amyloid polypetide hormone secreted by the pancreatic beta cells simultaneously with insulin in response to nutrient stimuli, that slows gastric emptying, reduces postprandial rises in blood glucose concentrations and improves A1C values. The FDA has approved pramlintide for use in patients with Type 1 and Type 2 diabetes. This non-insulin, injectable amylin analogue is administered by mealtime subcutaneous injection before meals, cannot be mixed with insulin in the same syringe and in patients with T1DM is not a replacement for but rather an addition to pre-meal insulin bolus injections.
Pramlintide regulates post-meal blood glucose levels by slowing gastric emptying.
Pramlintide regulates post-meal blood glucose levels by slowing gastric emptying and suppressing the abnormal postprandial rise of glucagon in patients with diabetes.(43) Thus, hepatic glucose production is better regulated. The effects on hepatic glucose production and increased insulin production are glucose-dependent and are overridden as serum glucose levels fall. In individuals with Type 1 diabetes, 30 to 60 mcg of pramlintide administered subcutaneously with meals resulted in sustained reductions in A1C with modest reductions in body weight.(44)(45) Hypoglycemia and nausea are the most commonly reported side effects. Nausea generally dissipates with time and can be minimized by slow upward dose titration.
Medical Nutritional Therapy
Just as there is no single medical regimen that fits all patients, there are no ADA diets that can be prescribed. An individualized nutrition care program must be customized to each patient's specific preferences and needs based on a comprehensive assessment. Integrating insulin therapy with an individual's food and activity preferences is central in the management and education of patients with Type 1 diabetes. While many issues are identified during the assessment phase, glycemic control is usually addressed first, followed by nutritional interventions related to improvement of dyslipidemia and blood pressure.
As we discussed in the previous Cyberounds® on this case, the T1DM patient must learn how to manage hypoglycemia not only for immediate safety but also because over-treating and/or fear of hypoglycemia are frequent barriers to reaching long-term glycemic goals. Some patients overeat and administer inadequate insulin in order to avoid hypoglycemia. These are not desirable strategies. While recognition and treatment of hypoglycemia are relatively straightforward, hypoglycemia prevention often requires detailed records and patient-provider teamwork. Patients need to learn the fine balance between food, exercise and medications as it relates to glycemia.
An important component of self-management is blood glucose monitoring. Choices of blood glucose monitors are plentiful; all meters are fast, and accurate when used correctly. Choosing one is based on individual preference and insurance reimbursement. Demonstration is effective in assessing technique and building patient confidence. The toll-free 800 number on the back of each monitor is useful for trouble shooting. Frequency and timing of testing need to be individualized according to the type of insulin regimen and changes in therapy. For instance, a patient with Type 1 diabetes who requires four injections or more will need to monitor at least four to eight times daily, while a patient requiring basal insulin only may not need to check their blood sugar more often that once or twice daily. Target blood sugar ranges need to be reviewed to interpret insulin effects and determine therapeutic changes.
Carbohydrate Counting
Bolus dosing before meals requires the advanced skill of carbohydrate counting for the purpose of determining the correct pre-meal dosage of rapid-acting insulin. The carbohydrate content of food can be found on a food label, in carbohydrate counting books and apps, or by learning that fixed serving sizes for each carbohydrate food contains 15 grams of carbohydrate. For example, one small piece of fruit or half a large piece of fruit each contains 15 grams. Some studies, including the DAFNE program, examining type 1 diabetics have shown significant improvements in HbA1c once taught carbohydrate counting programs, although many do not have control groups. (46)
Carbohydrates are the main nutrients that impact blood sugar, more so than proteins or fats.(38) A large meal of bacon and eggs has minimal carbohydrate content and, therefore, significantly less effect on blood sugar. The established theory has been that blood sugar rise is much more related to the total amount of carbohydrate than the source of carbohydrate.(38) For example, two slices of bread and six Mini Tootsie Rolls have the same carbohydrate content and, therefore, raise blood sugar similarly. However, the body of research is growing indicating that glycemic index, and thus the type of carbohydrate, may also play a large role in the glucose peak and length of glucose excursion.(46) Glycemic control can be achieved regardless of the amount or type of carbohydrate ingested as long as adequate insulin is administered. The most common carbohydrate counting mistakes by patients are identifying carbohydrate sources incorrectly, estimating portions incorrectly, misreading labels and snacking without administering insulin.
The correct answer is: "10 units." As the patient's CIR is one unit rapid-acting insulin for every 10 grams of carbohydrate, 9 units are needed for the 90-gram breakfast. Since the patient needs to drop 40 mg/dl to reach the pre-meal target of 100 mg/dl, an additional unit is required since one unit drops his blood sugar by 40 mg/dl (CF = 40).
Nine units may result in hyperglycemia. As the patient's CIR is one unit rapid-acting insulin for every 10 grams of carbohydrate, nine units are needed for the 90-gram breakfast. Since the patient needs to drop 40 mg/dl to reach the pre-meal target of 100 mg/dl, an additional unit is required since 1 unit drops his blood sugar by 40 mg/dl (CF = 40).
Eleven units may cause the patient to go low. As the patient's CIR is one unit rapid-acting insulin for every 10 grams of carbohydrate, nine units are needed for the 90-gram breakfast. To correct for the high pre-meal blood sugar and reach the target of 100 mg/dl, an additional unit of insulin is needed to drop the sugar 40 m/dl (CF = 40).
Cream cheese contains minimal carbohydrate. Carbohydrate is the main nutrient that impacts blood sugar, not protein or fat.
Individuals vary considerably in the amount of insulin needed for a fixed amount of carbohydrate. A commonly used method for estimating a patient's individualized carbohydrate to insulin ratio (CIR), the amount of carbohydrate that one unit of rapid acting insulin will cover, is to divide 500 by the average number of total daily units of insulin (rapid and long-acting) administered each day.(*) A patient on an average of 30 units of insulin per day would have a CIR of about 15:1 (500 divided by 30 equals 16.6). In other words, one unit of rapid-acting insulin is needed for 15 grams of carbohydrate. Factors that affect insulin sensitivity can change an individual's CIR. For instance, exercise will improve insulin sensitivity. An individual with a CIR of 15:1 who anticipates eating two cups of rice (90 grams of carbohydrate) needs six units of rapid acting insulin. Once exercise is discontinued, the individual's sensitivity may decrease and the same two cups of rice would now require more insulin. A rise in blood sugar from a meal of more than 50 mg/dl may be a sign of either incorrect carbohydrate counting or an incorrect CIR. More recent research has shifted from looking solely at CIR to adjusting insulin based on the glycemic index rather than carbohydrates alone. (46)
A commonly used method for estimating a patient's individualized carbohydrate to insulin ratio (CIR).
In addition to the insulin dose needed to cover the carbohydrate, a supplemental dose may be required to correct for a high pre-meal blood sugar. This dose is referred to as the correction factor (CF) or the amount that one unit of insulin can be expected to decrease the level of glucose. The CF can be estimated by dividing the total number of units of daily insulin into 1500.(39) For example, someone who requires a total daily insulin dose of 50 units can have their insulin sensitivity factor calculated by the following: 1500/TDD = 1500/50 amounts to 30 (one unit of insulin will drop the blood sugar by 30 mg/dl). An individual with a target pre-meal blood sugar of 100 mg/dl whose CF is 40 (one unit of rapid acting insulin drops the blood sugar 40 mg/dl) and whose pre-meal CBG is 180 mg/dl, needs an additional two units above and beyond the amount of insulin calculated to cover the anticipated amount of carbohydrate. For those individuals who find advanced carbohydrate counting too difficult, a fixed dose regimen (to a greater or lesser extent) can be provided. This, however, imposes the challenge of consistency in timing and carbohydrate content of meals.
Without detailed blood sugar, food, exercise and insulin-dosing records, it is difficult to identify problems and make appropriate therapeutic changes. A three-day record can provide enough of a glimpse into the complex but typically patterned lifestyle of each individual. To achieve successful treatment adherence, the health care provider must stress to their patient the importance of meaningful and engaged office visits. The rigor of intensive insulin therapy demands repeated visits by the patient and negotiations among team members. Good practice for intensive insulin therapy also requires multiple visits to a registered dietitian, preferably a CDE, during the first three months totaling three to four hours, as well as four to six additional hours of follow-up during the year. Attention to dietary management of lipids, blood pressure and weight require additional visits.
The correct answer is: "Dosing insulin based on desired meal."
The advantage of intensive insulin therapy using carbohydrate counting is the ability to achieve glycemic control without compromising flexibility in timing and content of meals. Glycemic control can be achieved even when skipping meals or eating more than usual. Of course, chronic overeating will result in weight gain. Patients learn to adjust their rapid acting insulin doses before meals according to the amount of carbohydrate they eat. Often, patients who carbohydrate count need to be reminded that high blood sugars from a meal are not from "too much" carbohydrate but rather arise as a result of inadequate insulin.
The advantage of intensive insulin therapy using carbohydrate counting is the ability to achieve glycemic control without compromising flexibility in timing or content of meals. Patients on fixed dose regimens of rapid acting insulins need to eat fixed amounts of carbohydrate; this regimen is seldom kept by the majority for prolonged periods of time, affects quality of life and rarely achieves optimal glycemic control.
It is the total amount of carbohydrate and not the source that impacts on blood sugars. As long as one counts carbohydrates and takes the corresponding amount of insulin to match the carbohydrate, glycemic control can be achieved. In practice, drinking large amounts of sugary beverages can be hard to manage due to the high caloric intake.
The advantage of intensive insulin therapy using carbohydrate counting is the ability to achieve glycemic control without compromising flexibility in timing or content of meals. On the other hand, patients on fixed combinations need to eat fixed amounts of carbohydrate at regular times in order to match the peaks of the insulins injected.
Glycemic index of foods does not impact as much on blood sugars as the total amount of carbohydrate.
Continuous Glucose Monitoring Sensor (CGMS)
CGMS is used when more intensive monitoring is required. These systems are usually comprised of a sensor, a transmitter and a receiver.(47) A glucose sensor, placed under the abdominal skin, measures interstitial glucose every 10 seconds and these glucose values are averaged every five minutes. These measurements are highly correlated with finger stick values.(40) The information from the sensor is sent to the transmitter which is connected to the sensor but sits on the skin. The information is relayed from transmitter wirelessly to the receiver which can be a dedicated device, smart phone, or insulin pump.(47)
The results can be read in real time, on demand or downloaded to a computer where graphs and tables reveal glucose trends. These devices can be especially helpful in complicated situations such as hypoglycemia unawareness, gastroparesis, gestational diabetes, preconception, pregnancy and lactation where the patient and doctor want to achieve tighter control. By obtaining frequent glucose values, individuals can more readily see the effect of diet, exercise and medications in order to make the needed changes that will result in fewer glucose excursions.
Recent analyses have shown patients with Type 1 Diabetes reaching a lower A1c when using real time CGM vs. intermittent self-monitored blood glucose without significant increases in hypoglycemia.(14)(47) Evaluation of the JDRF-CGM Study Group also showed significant reductions in A1c with CGM and significant reductions in hypoglycemia.(48) A recent study in Sweden similarly showed significant improvements in A1c with CGM compared to conventional therapy, and additionally improved well-being in the CGM group.(49) The American Association of Clinical Endocrinologists and American College of Endocrinology recently released a consensus statement regarding CGM stating: "CGM improves glycemic control, reduces hypoglycemia, and may reduce overall costs of diabetes management. Therefore, expanding CGM coverage and use would improve the health of the diabetes population."(50)
The correct answer is: "Two hours after each meal."
The mean blood glucose concentration obtained postprandially (one to two hours after a meal) primarily reflects the effectiveness of the bolus insulin dose. Postprandial values indicate if adequate bolus insulin was given to match the amount of carbohydrate consumed.
The mean blood glucose concentration before meals (before breakfast, before lunch and before dinner) primarily reflects the effectiveness of the basal insulin.
A nocturnal test reflects the effectiveness of the basal insulin overnight. It is common to see a sharp rise in blood glucose beginning at 2:00AM-3:00 AM from the dawn phenomenon.
The fasting blood glucose level reflects the adequacy of the overnight basal insulin.
The blood glucose level post exercise may reflect either basal or bolus excess, depending upon when the exercise took place. Generally, if the activity takes place within three hours after eating, a 50% reduction of mealtime insulin should be recommended. If the exercise takes place before the meal or lasts longer than 30 minutes, a reduction in basal insulin for 24-48 hours may be necessary, as glucose levels may be affected up to 48 hours later. To prevent hypoglycemia, extra carbohydrate calories may also be necessary prior to exercising.
Continuous Subcutaneous Insulin Infusion (CSII)
Insulin delivered via CSII is absorbed better and more predictably.
Continuous subcutaneous insulin infusion (CSII) a method of delivering insulin through a motor driven reservoir into a self-inserted subcutaneous infusion set; the insulin serves as both basal and bolus. All rapid-acting insulin analogues are more effective than regular insulin in insulin pumps — they achieve better glycemic reductions in postprandial blood glucose concentrations and provoke fewer episodes of hypoglycemia compared with regular insulin.(41)(42) The basal insulin consists typically of 40-60% of the total daily dose and is individually programmed and adjusted by 0.05 units every 30 minutes to match the changes in basal needs throughout the 24-hour day. Insulin delivered via CSII is absorbed better and more predictably than the "depot" of insulin delivered in multiple daily injections (MDI).(14)
The pre-meal bolus insulin amount can be automatically calculated by programming the pump for the patient with pertinent figures including the carbohydrate to insulin ratio, correction factor, glycemic targets and duration of insulin action. The patient enters the anticipated carbohydrate amount and blood sugar. The calculation takes into account the active insulin on board, subtracting this insulin from the estimated correction dose, thereby avoiding stacking of insulin and hypoglycemia. Pump features that promote individualization include bolus delivery over an extended period to match prolonged digestion and absorption of food. For example, a high fat meal treated with an injection of rapid-acting insulin often results in an initial hypoglycemic response followed by hyperglycemia when the food finally is finally absorbed.
Some studies comparing MDI to CSII demonstrate comparable HbA1C values, though patients on CSII report less hypoglycemia, post-meal glucose excursions and better quality of life.(42) Although a meta-analyses looking at analogue CSII alone vs MDI found no difference in hypoglycemia levels in adults with Type 1 Diabetes.(51) Some disadvantages of the insulin pump are the higher cost for the pump and its supplies, increased skin infections at the insertion site and greater chance of mechanical problems such as interruption of insulin flow or pump failure that can lead to diabetic ketoacidosis (DKA). An early malfunction that is not recognized can lead to DKA within four to six hours. Therefore, it is imperative for all individuals using an insulin pump to test blood glucose levels frequently (no less then four to six times each day), be properly trained in the use of the pump and learn how to avoid and treat acute complications proactively. It is important that those who choose the pump as a delivery system clearly understand that the convenience of no injections is offset by many other responsibilities and that the pump is a delivery system that is only as effective as its user.
Figure 3. Illustration of Two Insulin Pumps.
Continuous Subcutaneous Insulin Infusion (CSII) - most recent development of the closed loop system
In September 2016 the FDA approved the first hybrid closed-loop system to automatically monitor and deliver insulin.(52) These systems provide a basic background amount of insulin based on feedback from glucose readings, while the patient still controls the pre-meal boluses. Studies with hybrid closed-loop systems show an increase in the time spent in in the glucose target range and a reduction in the time spent in the hypoglycemic range.(48)
This is a case of a 51-year-old male who developed Type 1 diabetes also known as Latent Autoimmune Diabetes of the Adult (LADA). In the first Cyberounds® on this case, we reviewed how to establish a correct diagnosis, the essentials of patient education and the importance of early and aggressive treatment. Here, we have discussed intensive insulin management using a team approach. The prescription of an effective basal-bolus regimen is intricate and requires a team effort that includes the patient, nurse, dietitian, endocrinologist and others. This labor-intensive endeavor needs to be individualized through trial and error. A variety of insulins including the more recent analogues enable better physiologic insulin replacement treatment, with the majority of patients being treated with a basal-bolus regimen. Proper adjustments of bolus insulin need to be done according to carbohydrate counting and the constant variations in insulin sensitivity.
In addition to traditional injectable insulin, the FDA has approved an injectable non-insulin amylin analogue and a non-injectable inhaled insulin. The wide choice of new medications and gadgetry include pen syringes, insulin pumps and better systems for monitoring, all of which have made management of Type 1 diabetes easier. These advances have improved insulin administration and adherence, reduced episodes of hypoglycemia and fostered a better quality of life for patients but they have only had a modest impact on glycemic control. The Continuous Glucose Monitoring Sensor (CGMS) has slowly evolved into a closed loop system where glucose sensors will provide feedback to implantable insulin pumps so as to deliver insulin requirements more precisely. It must always be remembered, however, that successful outcomes can only be achieved when effective team management and education are provided in combination with a patient who is proactively involved in self-management.


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Hiking through the Forest and Sandhills of Halsey, Nebraska | Engagement Session
These two are eloping later this year in Rocky Mountain National Park so when Dena inquired with me about shooting their engagement session I knew they'd be up for something adventurous! I have a list of a few locations around the state of Nebraska that are incredibly beautiful and unique for photos and from that list Dena and Ryan chose Halsey, Nebraska (Population 83)! This place is special to me because I used to live there right along the river. Fun fact: my class size when I lived there was 6. Yep, there were 6 of us. My grandma still lives nearby and my husband and I love visiting her Sandhills ranch.
If you'd like to book a Nebraska Sandhills adventure session with me, contact me and let me know you're interested in that location!


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What Information About You Is Online? The Internet is just not about funny memes or social media. The Internet is a cornerstone of business today, but business is not alone. Cybercriminals are making the Internet their home to cause you harm, steal valuable information and t
What Is Network Segmentation? Businesses that offer WiFi to their customers or have sensitive data needs should consider network segmentation as a necessary component of their IT solution. With network segmentation, your wireless services are separated into different parts, allowing you to better c


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Første weekenden i august indbydes til åbningsevent på Vojens DiscGolfPark®. Anledningen er udvidelsen af banen til 18 huller (par 66). Du får samtidigt lejlighed til at prøve DM banen i Gram dagen efter. To baner – én turnering.
Oracle 1Z0-144 Demo Download
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I just realised, that the code in my previous posts about Twitter plugins is broken. This is because Twitter has switched off the API v1. This means, all applications using it (and using my example code) have stopped working.
There is a relatively easy solution using the great TweetSharp package. It works very well (apart from a very minor formatting issue) and is pretty easy to use, which you will see in this post.
First of all you need a few keys from Twitter. Namely a ConsumerKey, a ConsumerSecret, an AccessToken and an AccessTokenSecret. You can get all this in your Twitter developer login area. I'm not sure, why it has to be quite so complicated, but that's how it is.
Next, you need the TweetSharp package which you can install via your NuGet package manager.
The complicated part is over, the rest is smooth sailing. This is the code to get some tweets: var api = new TwitterService("myConsumerKey", "myConsumerSecret");
api.AuthenticateWith("myAccessToken", "myAccessTokenSecret");
var tweets = api.ListTweetsOnUserTimeline(
new ListTweetsOnUserTimelineOptions()
ScreenName = "tkglaser",
Count = 3,
IncludeRts = true
This retrieves the last 3 Tweets (including Re-Tweets) from my timeline.
All that is left to do is stick the Tweets into your MVC model and display them in a view. This is quite easy as well:
@foreach (var tweet in Model.Tweets)
That's it, hope it all works for you as easily as it worked for me. I'll put up a little example as well at some point, or at least repair the old examples.
Web & Mobile Engineer, Founder, Lean Startup Enthusiast.