Pancreatic β-cell function relates positively to HDL functionality in well-controlled type 2 diabetes mellitus

BackgroundHigh density lipoproteins (HDLs) have been implicated in glucose homeostasis. Among subjects with normal fasting glucose (NFG), impaired fasting glucose (IFG) and Type 2 diabetes mellitus (T2DM) we tested whether pancreatic β-cell function relates to HDL functionality, as determined by HDL anti-oxidative capacity and cellular cholesterol efflux to plasma.Subjects and methodsHDL anti-oxidative capacity (inhibition of LDL oxidation in vitro), cellular cholesterol efflux (the ability of plasma to stimulate cholesterol efflux out of cultured fibroblasts obtained from a single human donor), glucose and insulin were determined in fasting plasma samples from 37 subjects with NFG, 36 with IFG and 22 with T2DM (no glucose lowering drug or insulin treatment; HbA1c 6.0 ± 1.0%). Homeostasis model assessment was used to estimate pancreatic β-cell function (HOMA-β) and insulin resistance (HOMAir).ResultsHOMA-β was lowest, whereas HOMAir was highest in T2DM (P < 0.01 and P < 0.001 vs. NFG). HDL anti-oxidative capacity and cellular cholesterol efflux did not differ significantly according to glucose tolerance category. In univariate analysis and after controlling for HOMAir both HDL anti-oxidative capacity (P < 0.05) and cellular cholesterol efflux (P < 0.01) were positively correlated with HOMA-β in T2DM, but not in NFG and IFG. In age-, sex- and HOMAir-adjusted analyses, T2DM status interacted positively with HDL anti-oxidative capacity (P = 0.001) and cellular cholesterol efflux (P = 0.042) on HOMA-β. HbA1c interacted similarly with HDL functionality measures on HOMA-β.ConclusionsPancreatic β-cell function relates to pathophysiologically relevant measures of HDL function in T2DM, but not in NFG and IFG. Better HDL functionality may contribute to maintenance of β-cell function in subjects with well-controlled T2DM.     

Fish oil,insulin sensitivity,insulin secretion and glucose tolerance in healthy people: Is there any effect of fish oil supplementation in relation to the type of background diet and habitual dietary intake of n-6 and n-3 fatty acids?

AimTo evaluate whether a moderate supplementation of long-chain n-3 fatty acids is able to modulate insulin sensitivity, insulin secretion, β-cell function and glucose tolerance in healthy individuals consuming a diet rich in either saturated or monounsaturated fat, also in relation to their habitual dietary intake of n-6 and n-3 fatty acid.Methods and resultsOne hundred and sixty-two healthy individuals were randomly assigned to follow either one of two isoenergetic diets for 3 months, one rich in monounsaturated fats and the other rich in saturated fats. Within each group there was a second randomisation to fish oil (n-3 fatty acids 3.6 g/day) or placebo. At the beginning and at the end of the treatment periods insulin sensitivity (SI), first phase insulin response (FPIR) and glucose tolerance (K_G-value) were evaluated by the intravenous glucose tolerance test (IVGTT).Fish oil did not have any effect on SI, FPIR, K_G-value and disposition index in either diet. Even after dividing subjects according to the median value of n-6/n-3 ratio of serum phospholipids at baseline, there was no change in SI (Δ SI 0.42 ± 0.34 on fish oil vs 0.14 ± 0.23 on placebo for those with n-6/n-3 <4.85; −1.03 ± 0.47 on fish oil vs −0.27 ± 0.32 on placebo for those with n-6/n-3 >4.85) (M ± SE), FPIR (Δ FPIR 135.9 ± 78.9 vs 157.2 ± 157.5 pmol/L; 38.8 ± 181.7 vs 357.1 ± 181.7 pmol/L), K_G-value (Δ K_G 0.14 ± 0.15 vs 0.12 ± 0.11; −0.32 ± 0.16 vs 0.15 ± 0.15) or disposition index (Δ disposition index 1465.4 ± 830.4 vs 953.8 ± 690.0; −1641.6 ± 1034.3 vs 446.6 ± 905.1). Considering the 75th percentile of n-6/n-3 ratio (5.82) the results on insulin sensitivity, insulin secretion and disposition index were confirmed, while, in this more extreme situation, n-3 fatty acid supplementation induced a significant deterioration of K_G-value (p = 0.02).ConclusionsIn healthy individuals a moderate supplementation of fish oil does not affect insulin sensitivity, insulin secretion, β-cell function or glucose tolerance. The same is true even when the habitual dietary intake of n-6 and n-3 fatty acids is taken into account.     

Bariatric surgery in obesity: changes of glucose and lipid metabolism correlate with changes of fat mass

Background and AimBariatric surgery induces significant weight loss and improves glucose metabolism in obese patients (BMI > 35 kg/m²). Our aim was to compare restrictive (LAGB, laparoscopic gastric banding) and malabsorptive approaches (BIBP, biliary-intestinal bypass) on the loss of fat-free mass (FFM), fat mass (FM), and on changes of glucose and lipid metabolism.Methods and ResultsBody composition (bio-impedance analysis, BIA), blood glucose (BG), insulin, triglycerides, total- and HDL-cholesterol, liver enzymes (AST and ALT) were measured at baseline and 1 year after surgery in patients undergoing LAGB, BIBP, and in diet-treated control patients. In the main study, with patients matched for initial BMI (43–55 kg/m², LAGB = 24, BIBP = 12, controls = 6), decreases of BMI, FM, BG and cholesterol were greater in patients with BIBP than with LAGB (p < 0.01), while decreases of FFM, insulin, HOMA-IR and triglycerides were similar. No effects on BMI, FM, FFM, BG, insulin, HOMA-IR or cholesterol were observed in the control patients. Decreases of BG, insulin, HOMA-IR, cholesterol and triglycerides correlated with FM but not with FFM decrease. Similar results were obtained in an additional study in patients with a different initial BMI (LAGB = 25, BIBP = 6, controls = 24) and when considering all subjects together. A decrease of liver enzymes (ALT) was greater with LAGB than with BIBP, and HDL-cholesterol increased with LAGB and decreased with BIBP.ConclusionBMI, FM, BG and cholesterol decrease more with malabsorptive than with restrictive surgery, while FFM, insulin, HOMA-IR and triglycerides decrease in a similar way. FFM loss is of low entity. Changes of glucose and lipid metabolism are proportional to a decrease of fat mass but not of fat-free mass.     

Effects on post-prandial glucose and AGE precursors from two initial insulin strategies in patients with Type 2 diabetes uncontrolled by oral agents

ObjectiveProgressive β-cell dysfunction in Type 2 diabetes results in the need for insulin therapy in many patients. Yet the best regimen to prescribe to patients transitioning from oral anti-hyperglycemic drugs (OADs) is not clear. We sought to compare the effects of two standard initial insulin strategies (basal insulin alone versus premixed insulin) on post-prandial glucose metabolism and precursors of advanced glycation end-products in patients with type 2 diabetes suboptimally controlled on OADs.Research Design and MethodsThis was a 6-month, open-label, single-center study using a cross-over design. 14 subjects were randomized to one of two protocols: once daily insulin glargine or twice-daily 75%/25% neutral protamine lispro/lispro mix. At 12 weeks, the subjects were crossed-over to the opposite protocol. During each period, insulin doses were titrated to target fasting blood glucose of 90–110mg/dL. At baseline and after the two 12-week treatment periods, subjects were studied in the Clinical Research Center; they consumed three liquid mixed isocaloric meals at 4-h intervals, and glucose, free fatty acids (FFA), lipids, and α-dicarbonyls (3-deoxyglucosone [3-DG] and methylglyoxal [MG]) were measured before and after each meal. Patient data were analyzed in the context of their assigned insulin strategy groups.ResultBoth insulin regimens led to a significant improvement in glycemic profiles, including fasting glucose and HbA1c, compared to baseline. However, mean post-prandial glucose was lower with lispro mix than with glargine (153 ± 36 vs. 199 ± 49 mg/dL, respectively; P = 0.001). Likewise, there was a reduction in both fasting (48 ± 13 vs. 57 ± 19, P = 0.047) and post-prandial (53 ± 19 vs. 63 ± 23; P = 0.007) 3DG levels with lispro mix as compared to glargine. No differences were noted in MG concentrations.ConclusionIn type 2 diabetes patients failing OAD therapy, an initial insulin regimen of twice daily premixed insulin results in significantly improved post-prandial glucose levels as well as a reduction in a precursor of AGEs. The effect of these two initial insulin regimens on long-term diabetic complications requires further study.     

Early impairment of beta-cell function and insulin sensitivity characterizes normotolerant Caucasian women with previous gestational diabetes

Background and aimsWomen with previous gestational diabetes (pGDM) are at high risk of developing type 2 diabetes mellitus. The aim of this study was to evaluate insulin action and insulin secretion in women with pGDM.Methods and resultsOne hundred and fifty-three pGDM women and 45 with normal glucose tolerance during pregnancy (controls) were studied 1–3 years after delivery. Insulin sensitivity (ISI) and β-cell secretory capacity (β-index) were derived from 75-g OGTT. Disposition Index was calculated as the product of β-index and ISI. One hundred and twenty-two pGDM were normotolerant (NGT) and 31 had impaired glucose regulation (IGR) i.e. impaired glucose tolerance and/or impaired fasting glucose. NGT-pGDM, as compared to controls, had significant impairment in insulin action (ISI: 5.46 ± 2.81 vs. 7.38 ± 3.68, P < 0.01) and insulin secretion (β-index: 4.68 ± 1.01 vs. 5.24 ± 0.82 pmol/min/m²; P < 0.01). A further impairment was apparent in IGR-pGDM for β-index (4.16 ± 1.09; P < 0.05). The disposition index was reduced in NGT-pGDM as compared to controls (33.9%) and further reduced in IGR-pGDM (28.6%, vs. NGT-pGDM; ANOVA P < 0.001). In women of normal weight, ISI and β-index were significantly (P < 0.01) impaired in NGT-pGDM compared to controls and further reduced in IGR-pGDM, although a more pronounced defect in insulin secretion was apparent in these women (β-index: 4.02 ± 0.9; P < 0.05).ConclusionsNormotolerant women with pGDM show both impairment in insulin secretion and action irrespective of body weight. A more pronounced defect in insulin secretion seems to characterize normal weight women while a more prominent defect in insulin action is found in overweight women.     

Efficacy and safety of an insulin infusion protocol during and after cardiac surgery

AimPerioperative tight blood glucose (BG) control using insulin therapy after major surgery is a difficult, time-consuming task that also raises some concerns over the risk of severe hypoglycaemia. The aim of the present prospective study was to evaluate the efficacy and safety of an insulin therapy protocol in use at our institution.MethodsA total of 230 consecutive patients (mean ± SD age: 67 ± 11 years; diabetic patients: n = 62) undergoing cardiac surgery (coronary artery bypass grafting: n = 137; 20% off-pump) or intrathoracic aortic (n = 10) surgery were included. BG control was managed according to an insulin therapy protocol, described by Goldberg et al. (2004) [11], in use for 6 months in our intensive care unit. Insulin infusion rate and frequency of BG monitoring were both adjusted according to: (1) the current BG value; (2) the previous BG value; and (3) the current insulin infusion rate. Efficacy was assessed by the percentage of time spent at the target BG level (100–139 mg/dL) intraoperatively and during the first 2 postoperative days (POD).ResultsAll patients received postoperative insulin therapy. Patients spent 57.3% and 69.7% of time within the BG target range on POD 1 and 2, respectively. The percentage of time was significantly higher in nondiabetics than in diabetics. Mean BG measurements per patient intraoperatively, on POD 1 and on POD 2 were 4 ± 1, 10 ± 2 and 7 ± 2, respectively. No patient experienced any severe hypoglycaemic events (BG < 50 mg/dL).ConclusionThis study showed that a BG target of 100–139 mg/dL can be safely achieved with an insulin therapy protocol that can be routinely used in everyday clinical practice.     

Association between leptin and its soluble receptor with cardiometabolic risk factors in a Brazilian population

BackgroundMost studies evaluating the conjoint effects of leptin and human soluble leptin receptor (hs-LR) on cardiometabolic risk factors have been conducted in well-characterized ethnic groups. We aimed to assess the associations of leptin and hs-LR with the cardiometabolic risk factors that reflect the components of metabolic syndrome (MetS) in a Brazilian population with varying degrees of adiposity.MethodsThis is a cross-sectional analysis of adult subjects (n = 173, age 45 ± 12 years, 124 women; body mass index [BMI] 35.6 ± 9.5 kg/m²) for association of leptin and its soluble receptor with cardiometabolic risk factors (glucose, BMI, waist circumference, hip circumference, blood pressure, insulin, cholesterol and triglycerides). Plasma hs-LR was measured by ELISA; insulin and leptin were determined by RIA. Metabolic syndrome was defined by NCEP/ATP III.ResultsLeptin was positively associated with blood pressure, BMI, waist circumference, hip circumference, triglycerides, glucose, insulin and HOMA and inversely correlated with HDL-cholesterol. The hs-LR exhibited inverse relationship with cardiometabolic risk factors (P ≤ 0.006), except for glucose and lipid parameters. Leptin increased, whereas hs-LR decreased, with increasing number of MetS components (P for trend < 0.001). In multivariable models, sex, BMI and insulin were independently associated with leptin, whereas age, sex, BMI and systolic blood pressure were the independent correlates of hs-LR.ConclusionIn a Brazilian population with complex interethnic admixture, levels of hs-LR and leptin were independently associated with systolic blood pressure and insulin, respectively. Leptin increased with increasing number of MetS components. In turn, hs-LR decreased as the number of MetS components increased.     

A one-year study comparing the efficacy and safety of rosiglitazone and glibenclamide in the treatment of type 2 diabetes

Background and aimThis study was designed to compare the efficacy of rosiglitazone and glibenclamide in individuals with type 2 diabetes over a 12-month period.Methods and resultsA total of 598 patients were randomized to double-blind treatment for 52 weeks with rosiglitazone 4 mg/d (n = 200), rosiglitazone 8 mg/d (n = 191) or glibenclamide (n = 207; dose adjusted up to 15 mg/d over the first 12 weeks according to clinical response). Changes in fasting plasma glucose (FPG), haemoglobin A_1c (HbA_1c), fasting insulin and its precursor peptides, and lipids were measured and safety was evaluated.Significant reductions in HbA_1c levels at 52 weeks compared with baseline were seen in all treatment groups (rosiglitazone 4 mg/d = −0.3%, P = 0.0003; rosiglitazone 8 mg/d = −0.5%, P < 0.0001; glibenclamide = −0.7%, P < 0.0001). Mean FPG levels were also significantly reduced in all treatment groups (rosiglitazone 4 mg/d = −1.4 mmol/l; rosiglitazone 8 mg/d = −2.3 mmol/l; glibenclamide = −1.7 mmol/l; P < 0.0001 vs. baseline for all treatments). Rosiglitazone therapy reduced plasma insulin, proinsulin, split proinsulin and free fatty acid levels compared with glibenclamide. Rosiglitazone improved insulin resistance while a worsening was seen with glibenclamide. Total:high-density lipoprotein cholesterol ratios were reduced with glibenclamide and unchanged with rosiglitazone. All treatments were generally well tolerated.ConclusionsThe efficacy of rosiglitazone 8 mg/d in improving glycaemic control in patients with type 2 diabetes is comparable to that of glibenclamide. However, rosiglitazone reduced insulin resistance and proinsulin levels whereas glibenclamide use was associated with an increase in fasting insulin and proinsulin. This suggests that in the long term, rosiglitazone may protect the β-cell whereas glibenclamide is likely to increase the burden.     

The multi-faceted outcomes of conjunct diabetes and cardiovascular familial history in type 2 diabetes

BackgroundFamilial history of early-onset CHD (EOCHD) is a major risk factor for CHD. Familial diabetes history (FDH) impacts β-cell function. Some transmissible, accretional gradient of CHD risk may exist when diabetes and EOCHD familial histories combine. We investigated whether the impact of such combination is neutral, additive, or potentiating in T2DM descendants, as regards cardiometabolic phenotype, glucose homeostasis and micro-/macroangiopathies.MethodsCross-sectional retrospective cohort study of 796 T2DM divided according to presence (Diab[+]) or absence (Diab[?]) of 1st-degree diabetes familial history and/or EOCHD (CVD(+) and (?)). Four subgroups: (i) [Diab(?)CVD(?)] (n = 355); (ii) [Diab(+)CVD(?)] (n = 338); (iii) [Diab(?)CVD(+)] (n = 47); and (iv) [Diab(+)CVD(+)] (n = 56).ResultsNo interaction on subgroup distribution between presence of both familial histories, the combination of which translated into additive detrimental outcomes and higher rates of fat mass, sarcopenia, _hsCRP and retinopathy. FDH(+) had lower insulinemia, insulin secretion, hyperbolic product, and accelerated hyperbolic product loss. An EOCHD family history affected neither insulin secretion nor sensitivity. There were significant differences regarding macroangiopathy/CAD, more prevalent in [Diab(?)CVD(+)] and [Diab(+)CVD(+)]. Among CVD(+), the highest macroangiopathy prevalence was observed in [Diab(?)CVD(+)], who had 66% macroangiopathy, and 57% CAD, rates higher (absolute-relative) by 23%–53% (overall) and 21%–58% (CAD) than [Diab(+)CVD(+)], who inherited the direst cardiometabolic familial history (p 0.0288 and 0.0310).ConclusionsA parental history for diabetes markedly affects residual insulin secretion and secretory loss rate in T2DM offspring without worsening insulin resistance. It paradoxically translated into lower macroangiopathy with concurrent familial EOCHD. Conjunct diabetes and CV familial histories generate multi-faceted vascular outcomes in offspring, including lesser macroangiopathy/CAD.     

β-Amyloid-induced cognitive dysfunction impairs glucose homeostasis by increasing insulin resistance and decreasing β-cell mass in non-diabetic and diabetic rats

Objectiveβ-Amyloid accumulation in the brain may impair glucose homeostasis in both the brain and peripheral tissues. The present study investigated whether β-amyloid deposition in the hippocampus impairs glucose homeostasis by altering insulin sensitivity, glucose-stimulated insulin secretion or β-cell mass.MethodsMale rats were divided into two groups: a non-diabetic sham group and a diabetic partial pancreatectomized (Px) group. Each group was then subdivided into three treatment groups that received intra-CA1 infusions of β-amyloid (25–35; AMY), β-amyloid (35–25; RAMY; non-plaque forming), or saline at a rate of 3.6 nmol/day for 14 days.ResultsAfter 4 weeks, cognitive function measured by passive avoidance and water maze tests was impaired in non-diabetic rats that received AMY compared with rats that received saline or RAMY. Furthermore, diabetes exacerbated cognitive dysfunction in AMY-infused rats. This was associated with the hyperphosphorylation of tau as a result of attenuated insulin signaling (pAkt→pGSK) through decreased phosphorylation of cAMP responding element binding protein in the hippocampus of non-diabetic and diabetic rats. AMY exacerbated whole-body and hepatic insulin resistance in non-diabetic and diabetic rats. However, AMY potentiated glucose-stimulated insulin secretion in non-diabetic and diabetic rats, but caused decreased β-cell mass via increased β-cell apoptosis and decreased β-cell proliferation. As a result, glucose homeostasis was maintained by potentiating insulin secretion in diabetic rats, but may not be sustainable with further decreases in β-cell mass.ConclusionCognitive dysfunction attributable to β-amyloid accumulation in the hippocampus might be related to disturbed glucose homeostasis due to increased insulin resistance and decreased β-cell mass.     

Physical activity and blood lipids in rural and urban Tanzanians

BackgroundPhysical inactivity and raised blood lipids are two powerful risk factors for coronary heart disease (CHD). Incidence and mortality from CHD are expected to increase in developing countries. However, studies on the prevalence of cardiovascular risk factors in Africa are rare. In this study we examined the level of physical activity and serum lipids in rural and urban Tanzanians.MethodsRural and urban inhabitants, n = 985, mean age 43.8 years [SD, ±8.9] were investigated. Physical activity level (PAL) was assessed by an interview-administered questionnaire and blood samples were collected and analysed for serum lipids.ResultsThe rural population (n = 501) reported a substantially higher PAL than the urban population (n = 484). They also had significantly lower mean weight, body mass index (BMI), T-cholesterol, LDL-cholesterol, and HDL-cholesterol, T-cholesterol/HDL-cholesterol ratio, triglycerides and Apolipoprotein A-1.ConclusionThis study demonstrates that the urban Tanzanians have a considerably lower physical activity level and a more unfavourable lipid pattern than rural Tanzanians. These findings underline the importance of undertaking preventive measures to counter the increasing incidence of CHD in urban African populations.     

Type 1 diabetes: Dealing with physical activity

AimFor patients with type 1 diabetes (T1D) using multiple insulin injections (MII), there are currently no guidelines for insulin dose adjustments in the event of physical activity (PA) and no simple algorithms that can be applied directly. Thus, the objective of this study was to assess the relevance of simple algorithms based on assessments of PA intensity by T1D patients themselves.MethodsThis 4-month observational study was conducted in 35 patients using the Diabeo software system. Algorithms for insulin dose adjustments aimed to reduce the insulin dose of the meal closest to PA by 30 and 50% for moderate and intense PA, respectively. A 50% reduction plus extra carbohydrates was proposed for intense PA of long duration. These algorithms were entered into the Diabeo system.ResultsThe mean blood glucose (BG) profile in the event of PA (n = 151 triple BG values) was compared with that when no PA was performed (n = 3606). The initial mean FBG values were similar in both groups (7.58 ± 2.70 mmol/L vs. 7.80 ± 3.49 mmol/L; P = 0.36), whereas there was a slight, but significant, increase in 2-hours postprandial BG (PPBG) values related to PA, with a return to similar values before the next meal. The incidence of mild hypoglycaemia was similar, whether PA was undertaken or not, for the 2-hour PPBG and the next fasting/premeal glucose values.ConclusionThis appears to be a pragmatic and efficient method for T1D patients using MII to adjust insulin doses in the event of PA that only requires an assessment of PA intensity by the patients themselves to anticipate the magnitude of the reduction in insulin doses.     

Glycemic Status and Incident Heart Failure in Elderly Without History of Diabetes Mellitus: The Health, Aging, and Body Composition Study

BackgroundIt is unclear whether measures of glycemic status beyond fasting glucose (FG) levels improve incident heart failure (HF) prediction in patients without history of diabetes mellitus (DM).Methods and ResultsThe association of measures of glycemic status at baseline (including FG, oral glucose tolerance testing [OGTT], fasting insulin, hemoglobin A_1c [HbA_1c] levels, and homeostasis model assessment of insulin resistance [HOMA-IR] and insulin secretion [HOMA-B]) with incident HF, defined as hospitalization for new-onset HF, was evaluated in 2386 elderly participants without history of DM enrolled in the Health, Aging, and Body Composition Study (median age, 73 years; 47.6% men; 62.5% white, 37.5% black) using Cox models. After a median follow-up of 7.2 years, 185 (7.8%) participants developed HF. Incident HF rate was 10.7 cases per 1000 person-years with FG <100 mg/dL, 13.1 with FG 100–125 mg/dL, and 26.6 with FG ≥126 mg/dL (P = .002; P = .003 for trend). In adjusted models (for body mass index, age, history of coronary artery disease and smoking, left ventricular hypertrophy, systolic blood pressure and heart rate [HR], and creatinine and albumin levels), FG was the strongest predictor of incident HF (adjusted HR per 10 mg/dL, 1.10; 95% CI, 1.02–1.18; P = .009); the addition of OGTT, fasting insulin, HbA_1c, HOMA-IR, or HOMA-B did not improve HF prediction. Results were similar across race and gender. When only HF with left ventricular ejection fraction (LVEF) ≤40% was considered (n = 69), FG showed a strong association in adjusted models (HR per 10 mg/dL, 1.15; 95% CI, 1.03–1.29; P = .01). In comparison, when only HF with LVEF >40%, was considered (n = 71), the association was weaker (HR per 10 mg/dL, 1.05; 95% CI; 0.94–1.18; P = .41).ConclusionsFasting glucose is a strong predictor of HF risk in elderly without history of DM. Other glycemic measures provide no incremental prediction information.     

Improvement in β-cell function after diet-induced weight loss is associated with decrease in pancreatic polypeptide in subjects with type 2 diabetes

ObjectiveThe aim of our study was to evaluate the effect of a lifestyle intervention program on β-cell function and to explore the role of gastrointestinal peptides in subjects with T2D.MethodsSubjects with T2D (n = 74) received 24 weeks of intervention: 12 weeks of slimming diet (? 500 kcal/day) and the subsequent 12 weeks of diet were combined with aerobic exercise. All subjects were examined at weeks 0, 12 and 24. β-cell function was assessed during standard meal tests. Insulin secretory rate (ISR) was calculated by C-peptide deconvolution, and β-cell function was quantified with a mathematical model. Plasma concentrations of gastrointestinal peptides were measured in a fasting state and during hyperinsulinemia induced by hyperinsulinemic isoglycemic clamp.ResultsMean weight loss was 5.03 ± 4.38 kg (p < 0.001) in weeks 0–12. Weight did not change significantly in weeks 12–24. Both insulin secretion at the reference level and glucose sensitivity increased in weeks 0–12 (by 33% ± 54% and by 26% ± 53%, respectively, p < 0.001) and remained unchanged in weeks 12–24. Both fasting and hyperinsulinemic plasma concentrations of pancreatic polypeptide (PP) decreased in weeks 0–12 (p < 0.05 for both) and did not change significantly in weeks 12–24. Changes in insulin secretion at the reference level correlated negatively with plasma concentrations of PP during hyperinsulinemia (r = ? 0.36; p < 0.001). Changes in glucose sensitivity correlated negatively with changes in plasma concentrations of PP, both in fasting and during hyperinsulinemia (r = ? 0.2; p = 0.01 for both). The correlations remained significant after adjustment for changes in body-mass-index.ConclusionsAfter diet-induced weight loss, β-cell function improved in T2D subjects and remained unchanged after the addition of exercise. We demonstrate for the first time that these changes are associated with a decrease in PP secretion.     

Diabetes in Mozambique: prevalence, management and healthcare challenges

AimThe growing trend towards and deficient management of diabetes in Africa are important public-health challenges requiring surveillance. For this reason, this study aimed to assess the prevalence and awareness of diabetes in urban and rural Mozambique, and to describe its management.MethodsIn 2005, a representative sample of the national Mozambican adult population (n = 2343) was evaluated, according to the STEPwise approach to chronic disease risk factor surveillance (STEPS). Twelve-hour fasting blood glucose (FBG) was measured, using fingertip capillary whole blood, to estimate the prevalence of impaired fasting glucose (IFG; FBG ≥ 5.6 mmol/L and less than 6.1 mmol/L) and diabetes (FBG ≥ 6.1 mmol/L, or treatment with insulin and/or oral blood glucose-lowering drugs). Patients’ awareness and management of diabetes were assessed by questionnaire.ResultsThe prevalence of diabetes and IFG was 2.9% [95% confidence interval (95%CI): 1.8–4.0] and 2.5% (95%CI: 1.3–3.7), respectively. Diabetes was more frequent among urban dwellers (OR = 2.92, 95%CI: 1.45–5.86), mostly due to urban–rural differences in age, education, body mass index (BMI) and waist circumference (adjusted OR = 2.27, 95%CI: 0.83–6.26). In all, 13% of those with diabetes were aware of their condition, 10.9% had undergone glycaemia determination during the previous year, and 9% were being treated with oral blood glucose-lowering drugs and 3% with insulin.ConclusionDiabetes prevalence is low in Mozambique, but most diabetic patients were neither aware of their condition nor being treated pharmacologically, thus posing serious challenges to the provision of adequate care in an already disadvantageous context.     

Women with normal glucose tolerance and a history of gestational diabetes show significant impairment of β-cell function at normal insulin sensitivity

ObjectiveAlthough the nature of gestational diabetes mellitus (GDM) remains unclear, the condition is thought to be related primarily to insulin resistance, overweight and obesity. Most studies include women with a history of GDM and later carbohydrate metabolism abnormalities, while reports of women with previous GDM and subsequent normoglycaemia are scarce. The aim of this study was to assess insulin resistance and β-cell function in normoglycaemic women with a history of GDM.Materials and methodsThe study group included 199 women, aged 38.4 ± 6.6 years, diagnosed with GDM within the last 5–12 years [GDM(+)] and a control group of 50 comparable women in whom GDM was excluded [GDM(−)], according to WHO criteria. Blood glucose and insulin levels were measured at the beginning (fasting) and at 60 and 120 min of oral glucose tolerance tests. Indices of insulin resistance (HOMA-IR), insulin sensitivity (HOMA-S%) and β-cell function (HOMA-B%) were calculated.ResultsNormoglycaemia was observed in 57% of GDM(+) and 88% of GDM(−) women (P = 0.0003). Diabetes was diagnosed in 13 (6.5%) GDM(+) women and in none of the GDM(−) women. Comparison of 113 normoglycaemic GDM(+) and 44 normoglycaemic GDM(−) women revealed significantly impaired β−cell function (HOMA-B%: 131.1 ± 51.1 vs 144.7 ± 47.1, respectively; P = 0.038) with similar normal body mass index (BMI) and no differences in HOMA-IR and HOMA-S%.ConclusionIn this study, more than half of the GDM(+) women were presented with normal glucose tolerance. However, despite normoglycaemia, women with a history of GDM were characterized by significantly impaired insulin secretion, but no signs of increased insulin resistance.     

Calcium consumption and insulin resistance syndrome parameters. Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR)

Background and aimA number of studies have investigated the role of dietary calcium in lipid metabolism and weight regulation, and the influence of dairy products on the incidence of insulin resistance syndrome. In this study we have examined the relationship between dietary calcium and the established parameters of the insulin resistance syndrome.Methods and resultsThe study population (n = 4372) was taken from the DESIR (Data from the Epidemiological Study on the Insulin Resistance Syndrome) cohort. Data for parameters relating to the syndrome were recorded, including glucose, serum insulin, triglycerides, HDL-cholesterol, waist circumference and blood pressure. Total energy, calcium and alcohol intake were estimated using a food-frequency questionnaire. Relationships between dietary calcium density and the above parameters were analyzed by multiple linear regression models, adjusted for age, smoking, alcohol consumption and physical activity. From one quartile of calcium density to the next, mean systolic and diastolic blood pressures and insulin concentrations decreased in women by 0.9 mmHg, 0.5 mmHg and 2.4%, respectively, and HDL-cholesterol increased by 0.007 mmol/l (all p < 0.05) after adjustment for age, smoking, alcohol intake and physical activity. In men, there was an increase of 0.2 kg/m² in the body mass index(BMI) and a decrease of 0.4 mmHg in diastolic blood pressure (both p < 0.05).ConclusionsThese results confirm a beneficial association between dietary calcium and arterial blood pressure, insulin and HDL-cholesterol levels in women, whereas in men there was only a beneficial association with diastolic blood pressure.     

A sequential two meal challenge reveals abnormalities in postprandial TAG but not glucose in men with increasing numbers of metabolic syndrome components

ObjectiveTo examine the impact of increasing numbers of metabolic syndrome (MetS) components on postprandial lipaemia.MethodsHealthy men (n = 112) underwent a sequential meal postprandial investigation, in which blood samples were taken at regular intervals after a test breakfast (0 min) and lunch (330 min). Lipids, glucose and insulin were measured in the fasting sample, with triacylglycerol (TAG), non-esterified fatty acids and glucose analysed in the postprandial samples.ResultsSubjects were grouped according to the number of MetS components regardless of the combinations of components (0/1, 2, 3 and 4/5). As expected, there was a trend for an increase in body mass index, blood pressure, fasting TAG, glucose and insulin, and a decrease in fasting high-density lipoprotein cholesterol with increasing numbers of MetS components (P ≤ 0.0004). A similar trend was observed for the summary measures of the postprandial TAG and glucose responses. For TAG, the area under the curve (AUC) and maximum concentration (max C) were significantly greater in men with ≥3 than <3 components (P < 0.001), whereas incremental AUC was greater in those with 3 than 0/1 and 2, and 4/5 compared with 2 components (P < 0.04). For glucose, max C after the test breakfast (0–330 min) and total AUC (0–480 min) were higher in men with ≥3 than <3 components (P ≤ 0.001).ConclusionsOur data analysis has revealed a linear trend between increasing numbers of MetS components and magnitude (AUC) of the postprandial TAG and glucose responses. Furthermore, the two meal challenge discriminated a worsening of postprandial lipaemic control in subjects with ≥3 MetS components.     

Basal insulin or premix analogue therapy in type 2 diabetes patients

BackgroundWe sought to compare the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) given twice daily with once-daily insulin glargine in patients with type 2 diabetes beginning insulin therapy and who did not use thiazolidinediones, which are contraindicated with insulin in the European Union, in a subpopulation (N = 157) of the INITIATE study.MethodsAt baseline, HbA_1c was ≥ 8.0% on ≥ 1000 mg/day metformin alone or in combination with other oral antidiabetic drugs (OADs; e.g. sulphonylurea or alpha-glucosidase inhibitors). Metformin was adjusted up to 2550 mg/day and other OADs were discontinued. Starting insulin doses were subsequently adjusted weekly for 26 weeks by algorithm-directed titration.ResultsThe proportion of patients achieving a HbA_1c below 7.0% at 28 weeks was greater with BIAsp 30 than with insulin glargine (65% vs 41%, P = 0.003). The mean reduction in HbA_1c was greater for BIAsp 30 than for insulin glargine: − 2.89 ± 1.6% vs − 2.46 ± 1.6%, respectively (P = 0.035). Postprandial glucose increments were lower for the BIAsp 30 group after breakfast (P = 0.003) and dinner (P = 0.033); post-lunch values were not significantly different. No major hypoglycemic episodes were recorded. Nocturnal hypoglycemia was reported by 25% of subjects in the BIAsp 30 group and by 10% in the insulin glargine group (P = 0.021). Weight gain was 5.6 ± 4.6 and 3.0 ± 4.3 kg (P = 0.0004) for BIAsp 30 and insulin glargine, respectively.ConclusionsBIAsp 30, given twice daily in combination with metformin, was more effective than insulin glargine, given once daily in combination with metformin, at controlling blood glucose in insulin-naïve patients with type 2 diabetes, but was associated with increased weight gain and minor hypoglycemic events.     

High plasma HDL-C attenuates stress hyperglycemia during acute phase of myocardial infarction

ObjectiveDuring myocardial infarction (MI), a transient decrease of both insulin sensitivity and secretion triggers stress hyperglycemia, which is followed by a substantial increase in mortality. Recent findings in cellular models indicate that HDL may act on glucose homeostasis by improving insulin sensitivity and secretion. In this study, we explored this potential effect in patients during the acute phase of MI.MethodsPlasma glucose, insulin and C-peptide were measured at admission in the first 24 h and on the fifth day after MI with ST-segment elevation in 183 consecutive non-diabetic patients. Patients were divided into HDL-C quartiles for the analyses (Q1: <31, Q2: 31–38, Q3: 38–47 and Q4: >47 mg/dL). The Homeostasis Model Assessment version 2 was used to assess insulin sensitivity (HOMA2S) and beta-cell function (HOMA2B).ResultsOn admission, no difference was found between the quartiles in glucose (p = 0.6), insulin (p = 0.6) or C-peptide (p = 0.5) levels, HOMA2S (p = 0.9) or HOMA2B (p = 1.0). On the fifth day there was a reduction in glucose levels whose intensity was directly proportional to the HDL-C quartile (p < 0.001). At the same time, there was a reduction in plasma insulin (p < 0.001) and C-peptides (p < 0.001) whose magnitude was inversely proportional to the HDL-C quartile. Consistently, the increase of HOMA2S (p < 0.001) and HOMA2B (p = 0.01) were also positively associated with HDL-C levels. Furthermore, plasma HDL-C levels were inversely and independently associated with blood glucose change during the acute phase.ConclusionThis study demonstrates the association between low plasma HDL-C levels and increased duration of stress hyperglycemia during MI and suggests in humans the interaction between HDL and insulin secretion and sensitivity.