S. J. Weisnagel

Effect of sitagliptin therapy on postprandial lipoprotein levels in patients with type 2 diabetes

Aim: Recent studies indicate that type 2 diabetes is associated with an increased secretion of both hepatic and intestinal lipoproteins, leading to the accumulation of atherogenic triglyceride (TG)‐rich lipoproteins. Sitagliptin is a selective inhibitor of dipeptidyl peptidase‐4 that has been shown to reduce fasting and postprandial glucose levels in patients with type 2 diabetes presumably through incretin hormone‐mediated improvements in islet function. The objective of the present study is to examine the effects of treatment with sitagliptin on postprandial lipid and incretin hormone levels as well as glucose homeostasis in patients with type 2 diabetes.

Improvements in glucose homeostasis in response to regular exercise are influenced by the PPARG Pro12Ala variant: results from the HERITAGE Family Study

Aims/hypothesisExercise training improves glucose homeostasis, but large inter-individual differences are reported, suggesting a role of genetic factors. We investigated whether variants either confirmed or newly identified as diabetes susceptibility variants through genome-wide association studies (GWAS) modulate changes in phenotypes derived from an IVGTT in response to an endurance training programme.MethodsWe analysed eight polymorphisms in seven type 2 diabetes genes (CDKAL1 rs7756992; CDKN2A and CDKN2B rs10811661 and rs564398; HHEX rs7923837; IGF2BP2 rs4402960; KCNJ11 rs5215; PPARG rs1801282; and TCF7L2 rs7903146) in a maximum of 481 sedentary, non-diabetic white individuals, who participated in a 20-week endurance training programme. Associations were tested between the variants and changes in IVGTT-derived phenotypes.ResultsThe only evidence of association with training response was found with PPARG rs1801282 (Pro12Ala). We observed that Ala carriers experienced greater increase in overall glucose tolerance (Δglucose disappearance index Ala/Ala 0.22 ± 0.22, Pro/Ala 0.14 ± 0.06, Pro/Pro 0.004 ± 0.03; p = 0.0008), glucose effectiveness (Ala/Ala 0.28 ± 0.41, Pro/Ala 0.44 ± 0.14, Pro/Pro 0.09 ± 0.06; p = 0.004), acute insulin response to glucose (Ala/Ala 64.21 ± 37.73, Pro/Ala −11.92 ± 40.30, Pro/Pro −46.30 ± 14.70; p = 0.03) and disposition index (Ala/Ala 551.8 ± 448.5, Pro/Ala 534.6 ± 218.3, Pro/Pro −7.44 ± 88.18; p = 0.003).Conclusions/interpretationCompared with Pro/Pro individuals, PPARG Ala carriers experienced greater improvements in glucose and insulin metabolism in response to regular endurance training. However, we did not find evidence of association between type 2 diabetes susceptibility variants recently identified through GWAS and glucose homeostasis response to exercise. Our results extend those of previous studies showing that Ala carriers appear to be more responsive to beneficial health effects of lifestyle interventions.

The Contribution of Visceral Adiposity and Mid-Thigh Fat-Rich Muscle to the Metabolic Profile in Postmenopausal Women

This study explored the relationship between muscle fat infiltration derived from mid‐thigh computed tomography (CT) scan, central fat distribution and insulin sensitivity in postmenopausal women. Mid‐thigh CT scans were used to measure low attenuation muscle surface (LAMS) (0–34 Hounsfield units (HU)), which represented a specific component of fat‐rich muscle. Whole‐body insulin sensitivity (M/I) was evaluated by an euglycemic‐hyperinsulinemic clamp. A group of 103 women aged 57.0 ± 4.4 years was studied. Women with higher levels of LAMS presented higher metabolic risk features, particularly elevated fasting, 2‐h plasma glucose (2hPG) concentrations and diminished M/I (P < 0.05). To further study the contribution of muscle fat infiltration and central adiposity on metabolic parameters, we divided the whole group based on the median of LAMS and visceral adipose tissue (VAT). As expected, the best metabolic profile was found in the Low‐LAMS/Low‐VAT group and the worst in the High‐LAMS/High‐VAT group. Women with Low‐LAMS/High‐VAT presented similar metabolic risks to those with High‐LAMS/High‐VAT. There was no difference between High‐LAMS/Low‐VAT and Low‐LAMS/Low‐VAT, which presents the most healthy metabolic and glycemic profiles as reflected by the lowest levels of cardiovascular disease risk variables. This suggests that High‐LAMS/Low‐VAT is also at low risk of metabolic deteriorations and that High‐LAMS, only in the presence of High‐VAT seems associated with deteriorated risks. Although increased mid‐thigh fat‐rich muscle was related to a deteriorated metabolic profile, VAT appears as a more important contributor to alterations in the metabolic profile in postmenopausal women.

Impaired fasting glucose vs. glucose intolerance in pre-menopausal women: distinct metabolic entities and cardiovascular disease risk?

Background  Impaired glucose tolerance (IGT) is associated with an increased cardiovascular disease risk. Less is known about cardiovascular disease risk among subjects with impaired fasting glucose (IFG) or with combined IFG and IGT.

Visceral adipose tissue accumulation and cardiovascular disease risk profile in postmenopausal women with impaired glucose tolerance or type 2 diabetes.

Objective  Women with impaired glucose tolerance (IGT) and type 2 diabetes (T2D) are more at risk of cardiovascular disease. The aim of this study was to test the hypothesis that increased visceral adipose tissue (VAT) could explain to a large extent alterations in the cardiovascular disease risk profile of postmenopausal women with IGT or T2D.

Discordances among different tools used to estimate cardiovascular risk in postmenopausal women.

BACKGROUND New cardiovascular disease (CVD) risk factors are being recognized and suggested to be included in CVD risk stratification. High-sensitivity C-reactive protein (hs-CRP) and the metabolic syndrome (MetS) are among these risk factors. However, CVD risk classification may be divergent when using different approaches. OBJECTIVES To compare differences in CVD risk estimation using the Framingham risk score (FRS), hs-CRP and the presence of the MetS in a group of 109 postmenopausal women in primary CVD prevention. METHODS The FRS and presence of the MetS were determined. CVD risk was evaluated with a cardiovascular point scoring system based on Framingham covariables and hs-CRP values (Womens Health Study [WHS] model). The estimated CVD risks based on hs-CRP levels and the WHS model were compared with the FRS. RESULTS Using the FRS, 99% of women (n=108) were determined to have a low CVD risk. The MetS was identified in 39.4% (n=43) of the women. When hs-CRP was used alone to estimate CVD risk, 37.6% (n=41) of women were classified as being at low, 33.9% (n=37) at moderate and 28.4% (n=31) at high CVD risk. With the WHS model, 83.5% (n=91), 14.7% (n=16) and 1.8 % (n=2) of women were classified as being at low, moderate and high CVD risk, respectively. CONCLUSIONS A substantial number of postmenopausal women showing evidence of the MetS were not identified by the FRS, even though women with the MetS are at higher risk of CVD. Estimation of risk by hs-CRP is significantly divergent when using conventional hs-CRP cutoff values compared with an integrated use in the WHS model.

Prospective study evaluating the use of nasal glucagon for the treatment of moderate to severe hypoglycaemia in adults with type 1 diabetes in a real‐world setting

In the present multicentre, open‐label, prospective, phase III study, we evaluated the real‐world effectiveness and ease of use of nasal glucagon (NG) in the treatment of moderate/severe hypoglycaemic events (HEs) in adults with type 1 diabetes (T1D). Patients and caregivers were taught how to use NG (3 mg) to treat moderate/severe HEs, record the time taken to awaken or return to normal status, and measure blood glucose (BG) levels over time. Questionnaires were used to collect information about adverse events and ease of use of NG. In the efficacy analysis population, 69 patients experienced 157 HEs. In 95.7% patients, HEs resolved within 30 minutes of NG administration. In all the 12 severe HEs, patients awakened or returned to normal status within 15 minutes of NG administration without additional external medical help. Most caregivers reported that NG was easy to use. Most adverse events were local and of low to moderate severity. In this study, a single, 3‐mg dose of NG demonstrated real‐life effectiveness in treating moderate and severe HEs in adults with T1D. NG was well tolerated and easy to use.

Trimester-Specific Dietary Intakes in a Sample of French-Canadian Pregnant Women in Comparison with National Nutritional Guidelines

Diet during pregnancy greatly impacts health outcomes. This study aims to measure changes in dietary intakes throughout trimesters and to assess pregnant women’s dietary intakes in comparison with current Canadian nutritional recommendations. Seventy-nine pregnant women were recruited and completed, within each trimester, three Web-based 24-h dietary recalls and one Web questionnaire on supplement use. Dietary intakes from food, with and without supplements, were compared to nutritional recommendations throughout pregnancy. Energy and macronutrient intakes remained stable throughout pregnancy. A majority of women exceeded their energy and protein requirements in the first trimester, and fat intakes as a percentage of energy intakes were above recommendations for more than half of the women in all trimesters. Supplement use increased dietary intakes of most vitamins and minerals, but 20% of women still had inadequate total vitamin D intakes and most women had excessive folic acid intakes. This study showed that pregnant women did not increase their energy intakes throughout pregnancy as recommended. Furthermore, although prenatal supplementation reduces the risk of inadequate intake for most micronutrients, there is still a risk of excessive folic acid and insufficient vitamin D intake, which needs further investigation.