Pioneering technique promises type 1 diabetes breakthrough

Research to better predict mealtime insulin doses

New University of Sydney research is taking a completely novel approach to insulin dosage, with the potential to make it easier for people with type 1 diabetes to adjust their insulin levels after a fatty meal.

Led by Dr Kirstine Bell from the University’s Charles Perkins Centre, the cutting-edge project will use an innovative bioengineering approach developed in conjunction with Harvard Medical School. Dr Bell’s team have successfully modelled blood glucose responses to meals of varying fat content and can accurately predict how much insulin is required to keep glucose levels within a tight optimal range.

The findings hold the promise of empowering people with type 1 diabetes with more accurate information on how to moderate insulin doses and reduce the risk of dangerous high and low blood glucose levels.

“Currently, mealtime insulin doses are calculated based solely on the amount of carbohydrate in the meal, despite recent studies showing dietary fat can increase insulin requirements by more than 40 percent,” said Dr Kirstine Bell, who is also a dietitian and credentialed diabetes educator.

“Traditionally whenever someone reports high blood glucose levels after a meal, it was assumed this was because they did something wrong: they didn’t calculate their carbs right or estimate their portion size correctly.

“Now we’re learning that we didn’t have all the information and we need to go back to the drawing board to learn more about what’s really happening in the body to create better solutions.”


Fat is the Cause of Type 2 Diabetes

Studies dating back nearly a century noted a striking finding: If you take young, healthy people and split them up into two groups—half on a fat-rich diet and half on a carbohydrate-rich diet—we find that within just two days, glucose intolerance skyrockets in the fat group. The group that had been shoveling fat in ended up with twice the blood sugar. As the amount of fat in the diet goes up, so does one’s blood sugar. Why would eating fat lead to higher blood sugar levels? It would take scientists nearly seven decades to unravel this mystery, but it would end up holding the key to our current understanding of the cause of type 2 diabetes.


What Causes Insulin Resistance?

This is the first of a 3-part video series on the cause of type 2 diabetes, so as to better understand dietary interventions to prevent and treat the epidemic. Next, in The Spillover Effect Links Obesity to Diabetes, I talk about how that fat can come either from our diet or excess fat stores, and then in Lipotoxicity: How Saturated Fat Raises Blood Sugar, I show how not all fats are equally to blame.


Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study.


Recent muscle biopsy studies have shown a relation between intramuscular lipid content and insulin resistance. The aim of this study was to test this relation in humans by using a novel proton nuclear magnetic resonance (1H NMR) spectroscopy technique, which enables non-invasive and rapid (approximately 45 min) determination of intramyocellular lipid (IMCL) content. Normal weight non-diabetic adults (n = 23, age 29+/-2 years. BMI = 24.1+/-0.5 kg/m2) were studied using cross-sectional analysis. Insulin sensitivity was assessed by a 2-h hyperinsulinaemic (approximately 450 pmol/l)-euglycaemic (approximately 5 mmol/l) clamp test. Intramyocellular lipid concentrations were determined by using localized 1H NMR spectroscopy of soleus muscle. Simple linear regression analysis showed an inverse correlation (r = -0.579, p = 0.0037) [corrected] between intramyocellular lipid content and M-value (100-120 min of clamp) as well as between fasting plasma non-esterified fatty acid concentration and M-value (r = -0.54, p = 0.0267). Intramyocellular lipid content was not related to BMI, age and fasting plasma concentrations of triglycerides, non-esterified fatty acids, glucose or insulin. These results show that intramyocellular lipid concentration, as assessed non invasively by localized 1H NMR spectroscopy, is a good indicator of whole body insulin sensitivity in non-diabetic, non-obese humans.


Rapid impairment of skeletal muscle glucose transport/phosphorylation by free fatty acids in humans.


The initial effects of free fatty acids (FFAs) on glucose transport/phosphorylation were studied in seven healthy men in the presence of elevated (1.44 +/- 0.16 mmol/l), basal (0.35 +/- 0.06 mmol/l), and low (<0.01 mmol/l; control) plasma FFA concentrations (P < 0.05 between all groups) during euglycemic-hyperinsulinemic clamps. Concentrations of glucose-6-phosphate (G-6-P), inorganic phosphate (Pi), phosphocreatine, ADP, and pH in calf muscle were measured every 3.2 min for 180 min by using 31P nuclear magnetic resonance spectroscopy. Rates of whole-body glucose uptake increased similarly until 140 min but thereafter declined by approximately 20% in the presence of basal and high FFAs (42.8 +/- 3.6 and 41.6 +/- 3.3 vs. control: 52.7 +/- 3.3 micromol x kg(-1) x min(-1), P < 0.05). The rise of intramuscular G-6-P concentrations was already blunted at 45 min of high FFA exposure (184 +/- 17 vs. control: 238 +/- 17 micromol/l, P = 0.008). At 180 min, G-6-P was lower in the presence of both high and basal FFAs (197 +/- 21 and 213 +/- 18 vs. control: 286 +/- 19 micromol/l, P < 0.05). Intramuscular pH decreased by -0.013 +/- 0.001 (P < 0.005) during control but increased by +0.008 +/- 0.002 (P < 0.05) during high FFA exposure, while Pi rose by approximately 0.39 mmol/l (P < 0.005) within 70 min and then slowly decreased in all studies. In conclusion, the lack of an initial peak and the early decline of muscle G-6-P concentrations suggest that even at physiological concentrations, FFAs primarily inhibit glucose transport/phosphorylation, preceding the reduction of whole-body glucose disposal by up to 120 min in humans.


Mechanism of free fatty acid-induced insulin resistance in humans.


To examine the mechanism by which lipids cause insulin resistance in humans, skeletal muscle glycogen and glucose-6-phosphate concentrations were measured every 15 min by simultaneous 13C and 31P nuclear magnetic resonance spectroscopy in nine healthy subjects in the presence of low (0.18 +/- 0.02 mM [mean +/- SEM]; control) or high (1.93 +/- 0.04 mM; lipid infusion) plasma free fatty acid levels under euglycemic (approximately 5.2 mM) hyperinsulinemic (approximately 400 pM) clamp conditions for 6 h. During the initial 3.5 h of the clamp the rate of whole-body glucose uptake was not affected by lipid infusion, but it then decreased continuously to be approximately 46% of control values after 6 h (P < 0.00001). Augmented lipid oxidation was accompanied by a approximately 40% reduction of oxidative glucose metabolism starting during the third hour of lipid infusion (P < 0.05). Rates of muscle glycogen synthesis were similar during the first 3 h of lipid and control infusion, but thereafter decreased to approximately 50% of control values (4.0 +/- 1.0 vs. 9.3 +/- 1.6 mumol/[kg.min], P < 0.05). Reduction of muscle glycogen synthesis by elevated plasma free fatty acids was preceded by a fall of muscle glucose-6-phosphate concentrations starting at approximately 1.5 h (195 +/- 25 vs. control: 237 +/- 26 mM; P < 0.01). Therefore in contrast to the originally postulated mechanism in which free fatty acids were thought to inhibit insulin-stimulated glucose uptake in muscle through initial inhibition of pyruvate dehydrogenase these results demonstrate that free fatty acids induce insulin resistance in humans by initial inhibition of glucose transport/phosphorylation which is then followed by an approximately 50% reduction in both the rate of muscle glycogen synthesis and glucose oxidation.


Low Carb Diets and Coronary Blood Flow

The reason I have so few videos about low carb diets, is that I already wrote a whole book about it! Carbophobia is now available free online full-text at Atkins’ lawyers threatened to sue, leading to a heated exchange I reprint on the site.

I did touch on low carb diets in my video Atkins Diet: Trouble Keeping It Up, though they don’t have to necessarily be that unhealthy (see my video Plant-Based Atkins Diet).


Lipotoxicity: How Saturated Fat Raises Blood Sugar

This is the third of a three-part series, starting with What Causes Insulin Resistance? and The Spillover Effect Links Obesity to Diabetes. I wish I could have fit it all into one video, but it would have just been too long.

Even if saturated fat weren’t associated with heart disease, its effects on pancreatic function and insulin resistance in the muscles would be enough to warrant avoiding it. Despite popular press accounts, saturated fat intake remains the primary modifiable determinant of LDL cholesterol, the #1 risk factor for our #1 killer–heart disease. See The Saturated Fat Studies: Buttering Up the Public and The Saturated Fat Studies: Set Up to Fail.

How low should we shoot for in terms of saturated fat intake? As low as possible, according to the U.S. National Academies of Science Institute of Medicine: Trans Fat, Saturated Fat, and Cholesterol: Tolerable Upper Intake of Zero.


Good Fats Vs. Bad Fats

Lisa Urquhart shows you which fats to try and which to ditch

The Good 

Monounsaturated and polyunsaturated fats have been linked to higher ‘good’ cholesterol (HDL) and decreased ‘bad’ cholesterol (LDL). Research suggests that eating these kinds of fats in moderation can improve your blood glucose levels and reduce your risk of developing heart disease.

You can find them in plant oils – olive, sunflower, canola, rice bran – as well as in nuts, fish, seeds, avocados and soy. These types of fats are also a staple of the Mediterranean diet, which is considered to be one of the healthiest diets in the world.