Lene S. Mortensen

Bodyweight Changes Associated with Antihyperglycaemic Agents in Type 2 Diabetes Mellitus

The majority of patients with type 2 diabetes mellitus are overweight or obese at the time of diagnosis, and obesity is a recognised risk factor for type 2 diabetes and coronary heart disease (CHD). Conversely, weight loss has been shown to improve glycaemic control in patients with type 2 diabetes, as well as to lower the risk of CHD. The traditional pharmacotherapies for type 2 diabetes can further increase weight and this may undermine the benefits of improved glycaemic control. Furthermore, patients’ desire to avoid weight gain may jeopardise compliance with treatment, thereby limiting treatment success and indirectly increasing the risk of long-term complications. This review evaluates the influences of established and emerging therapies on bodyweight in type 2 diabetes.

Effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile and inflammation markers in metabolic syndrome – a randomized study (SYSDIET)

Different healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and inflammatory markers in people with metabolic syndrome.

Liraglutide suppresses postprandial triglyceride and apolipoprotein B48 elevations after a fat-rich meal in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, cross-over trial

Postprandial triglyceridaemia is a risk factor for cardiovascular disease (CVD). This study investigated the effects of steady‐state liraglutide 1.8 mg versus placebo on postprandial plasma lipid concentrations after 3 weeks of treatment in patients with type 2 diabetes mellitus (T2DM).

Effects of different fractions of whey protein on postprandial lipid and hormone responses in type 2 diabetes

Background/Objectives:Exacerbated postprandial lipid responses are associated with an increased cardiovascular risk. Dietary proteins influence postprandial lipemia differently, and whey protein has a preferential lipid-lowering effect. We compared the effects of different whey protein fractions on postprandial lipid and hormone responses added to a high-fat meal in type 2 diabetic subjects.Subjects/Methods:A total of 12 type 2 diabetic subjects ingested four isocaloric test meals in randomized order. The test meals contained 100 g of butter and 45 g of carbohydrate in combination with 45 g of whey isolate (iso-meal), whey hydrolysate (hydro-meal), α-lactalbumin enhanced whey (lac-meal) or caseinoglycomacropeptide enhanced whey (CGMP-meal). Plasma concentrations of triglyceride, retinyl palmitate, free fatty acid, insulin, glucose, glucagon, glucagon-like peptide 1 and glucose-dependent insulinotropic peptide were measured before and at regular intervals until 8-h postprandially.Results:We found no statistical significant differences between meals on our primary variable triglyceride. The retinyl palmitate response was higher after the hydro-meal than after the iso- and lac-meal in the chylomicron-rich fraction (P=0.008) while no significant differences were found in the chylomicron-poor fraction. The hydro- and iso-meal produced a higher insulin response compared with the lac- and CGMP-meal (P<0.001). Otherwise no significant differences in the hormone responses were found in the incremental area under the curve over the 480-min period.Conclusions:A supplement of four different whey protein fractions to a fat-rich meal had similar effects on postprandial triglyceride responses in type 2 diabetic subjects. Whey isolate and whey hydrolysate caused a higher insulin response.

Acute differential effects of dietary protein quality on postprandial lipemia in obese non-diabetic subjects.

Non-fasting triglyceridemia is much closer associated to cardiovascular risk compared to fasting triglyceridemia. We hypothesized that there would be acute differential effects of four common dietary proteins (cod protein, whey isolate, gluten, and casein) on postprandial lipemia in obese non-diabetic subjects. To test the hypothesis we conducted a randomized, acute clinical intervention study with crossover design. We supplemented a fat rich mixed meal with one of four dietary proteins i.e. cod protein, whey protein, gluten or casein. Eleven obese non-diabetic subjects (age: 40-68, body mass index: 30.3-42.0 kg/m(2)) participated and blood samples were drawn in the 8-h postprandial period. Supplementation of a fat rich mixed meal with whey protein caused lower postprandial lipemia (P = .048) compared to supplementation with cod protein and gluten. This was primarily due to lower triglyceride concentration in the chylomicron rich fraction (P = .0293). Thus, we have demonstrated acute differential effects on postprandial metabolism of four dietary proteins supplemented to a fat rich mixed meal in obese non-diabetic subjects. Supplementation with whey protein caused lower postprandial lipemia compared to supplementation with cod and gluten. As postprandial lipemia is closely correlated to cardiovascular disease, long-term dietary supplementation with whey protein may prove beneficial in preventing cardiovascular disease in obese non-diabetic subjects.

Differential effects of dietary protein sources on postprandial low-grade inflammation after a single high fat meal in obese non-diabetic subjects

BackgroundObesity is a state of chronic low-grade inflammation. Chronic low-grade inflammation is associated with the pathophysiology of both type-2 diabetes and atherosclerosis. Prevention or reduction of chronic low-grade inflammation may be advantageous in relation to obesity related co-morbidity. In this study we investigated the acute effect of dietary protein sources on postprandial low-grade inflammatory markers after a high-fat meal in obese non-diabetic subjects.MethodsWe conducted a randomized, acute clinical intervention study in a crossover design. We supplemented a fat rich mixed meal with one of four dietary proteins - cod protein, whey isolate, gluten or casein. 11 obese non-diabetic subjects (age: 40-68, BMI: 30.3-42.0 kg/m2) participated and blood samples were drawn in the 4 h postprandial period. Adiponectin was estimated by ELISA methods and cytokines were analyzed by multiplex assay.ResultsMCP-1 and CCL5/RANTES displayed significant postprandial dynamics. CCL5/RANTES initially increased after all meals, but overall CCL5/RANTES incremental area under the curve (iAUC) was significantly lower after the whey meal compared with the cod and casein meals (P = 0.0053). MCP-1 was initially suppressed after all protein meals. However, the iAUC was significantly higher after whey meal compared to the cod and gluten meals (P = 0.04).ConclusionWe have demonstrated acute differential effects on postprandial low grade inflammation of four dietary proteins in obese non-diabetic subjects. CCL5/RANTES initially increased after all meals but the smallest overall postprandial increase was observed after the whey meal. MCP-1 was initially suppressed after all 4 protein meals and the whey meal caused the smallest overall postprandial suppression.Trial RegistrationClinicalTrials.gov ID: NCT00863564

Combining insulins with oral antidiabetic agents: effect on hyperglycemic control, markers of cardiovascular risk and disease

Patients with type 2 diabetes mellitus (T2DM) have an increased risk of cardiovascular disease (CVD). Unfortunately, several potential barriers exist for CVD risk management in diabetes, including the need for significant lifestyle changes, potential problems with hypoglycemia, weight gain, injection tolerability, treatment complexity with current diabetes therapies and other, unmodifiable factors. Improving glycemic control may impact CVD risk. Treatment of T2DM usually starts with lifestyle changes such as diet and exercise. When these become insufficient, pharmacotherapy is required. Various oral antidiabetic drugs (OADs) are available that reduce hyperglycemia. The first line of therapy is usually metformin, since it does not increase weight and seems to have a beneficial effect on CVD mortality and risk factors. As T2DM progresses, insulin treatment becomes necessary for the majority of patients. The last few years have seen the development of long-acting, rapid-acting, and premixed insulin analog formulations. The treat-to-target algorithms of recent studies combining OADs plus insulin analogs have demonstrated that patients can reach glycemic treatment targets with low risk of hypoglycemia, greater convenience, and – with some analogs – limited weight gain vs conventional insulins. These factors may possibly have a positive influence on CVD risk. Future studies will hopefully elucidate the benefits of this approach.

Acute differential effects of milk-derived dietary proteins on postprandial lipaemia in obese non-diabetic subjects.

Background/Objectives:Postprandial lipaemia is an established risk factor for atherosclerosis. To investigate the acute effect of four milk-derived dietary proteins (alpha-lactalbumin, whey isolate, caseinoglycomacropeptide and whey hydrolysate) on postprandial lipaemia, we have conducted a randomized, acute, single-blinded clinical intervention study with crossover design.Subjects/Methods:A total of 11 obese non-diabetic subjects (age: 44–74, BMI: 30–41.4 kg m-2) were included. On 4 different days the subjects ingested a high-fat meal with the following energy distribution: 66% energy from fat (100 g of butter), 15% of energy from carbohydrate (90 g of white wheat bread) and 19% of energy from protein (45 g of pure protein). Our primary variable was plasma triglyceride measured in the 8-h postprandial period. Secondarily, retinyl palmitate, non-esterified free fatty acids, glucose, insulin, glucagon, GLP-1 and GIP, active and total grehlin and cholecystokinin were measured.Results:We observed no statistically significant (P=0.8) differences between meals on our primary variable that is, triglycerides. Whey hydrolysate was associated with a significantly (P=0.02) smaller postprandial suppression of non-esterified free fatty acids compared with the other dietary proteins.Conclusion:We did not observe significant differences in postprandial lipaemia to the four milk-derived dietary proteins. Whey hydrolysate caused less postprandial suppression of free fatty acids.

Acute effects of casein on postprandial lipemia and incretin responses in type 2 diabetic subjects

BACKGROUND AND AIMS Exaggerated and prolonged postprandial lipemia is potentially atherogenic and associated with type 2 diabetes. Limited data exist regarding the influence of dietary protein on postprandial lipemia in type 2 diabetes. We investigated, over 8-h, the acute effects of casein alone or in combination with carbohydrate on postprandial lipid and incretin responses to a fat-rich meal in type 2 diabetes. METHODS AND RESULTS Eleven type 2 diabetic subjects ingested four test meals in random order: an energy-free soup plus 80 g of fat (control-meal); control-meal plus 45 g carbohydrates (CHO-meal); control-meal plus 45 g of casein (PRO-meal); and PRO-meal plus 45 g carbohydrates (CHO+PRO-meal). Triglyceride and retinyl palmitate responses were measured in plasma and in a chylomicron-rich and chylomicron-poor fraction. We found no significant differences in triglyceride responses to PRO- and CHO+PRO-meal compared to the control-meal. However, the addition of casein to the CHO-meal reduced the raised triglyceride response in the chylomicron-rich fraction. Retinyl palmitate responses did not differ significantly between meals in the chylomicron-rich fraction, whereas the PRO-meal increased retinyl palmitate in the chylomicron-poor fraction. PRO- and PRO+CHO-meal increased insulin and glucagon compared to the control-meal. PRO+CHO-meal increased the glucose-dependent insulinotropic peptide response while no change in glucagon-like peptide-1 responses was detected. CONCLUSIONS The data presented suggest that casein per se did not modulate the postprandial triglyceride response in type 2 diabetes. When added to carbohydrate, casein suppressed the triglyceride response in the chylomicron-rich fraction, increased insulin and glucagon but did not affect the incretin responses.

Can the Glycemic Index (GI) be used as a tool in the prevention and management of Type 2 diabetes

The large increase in type 2 diabetes (T2DM), the considerable lifetime risk of diabetes and the loss of lifetime call for concerted action to prevent T2DM and its complications. Since diabetes is characterized by abnormal glucose metabolism, the question arises of whether a high intake of carbohydrates that are rapidly absorbed as glucose may increase the risk and worsen the course of T2DM. To quantify the impact of carbohydrates on blood glucose the glycemic index (GI) and the glycemic load (GL) have been applied. The GI of a food is a method of ranking carbohydrate rich foods according to their glycemic responses. GI is defined as the incremental area under the blood glucose curve of 50g carbohydrate of a test food expressed as a percentage of the area of the response to an equivalent amount of a reference food (glucose or white bread). In relation to GI/GL and prevention of T2DM there is insufficient information from observational studies to determine whether a positive association exists or not. Only randomized controlled clinical intervention studies will be able to provide the final answer. From meta-analyses of randomised controlled clinical trials comparing low and high GI diets in the treatment of diabetes it has been found that low GI diets improve the glycemic control. Labeling of foods with GI would be helpful for persons with diabetes, but the usefulness for healthy subjects remains to be clarified. At present it seems premature to introduce GI labeling for the entire population.