Efficacy of liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, on body weight, eating behavior, and glycemic control, in Japanese obese type 2 diabetes

ABSTRACT: BACKGROUND: We recently reported that short-term treatment with liraglutide (20.0 +/- 6.4 days) reduced body weight and improved some scales of eating behavior in Japanese type 2 diabetes inpatients. However, it remained uncertain whether such liraglutide-induced improvement is maintained after discharge from the hospital. The aim of the present study was to determine the long-term effects of liraglutide on body weight, glycemic control, and eating behavior in Japanese obese type 2 diabetics. METHODS: Patients with obesity (body mass index (BMI) >25 kg/m2) and type 2 diabetes were hospitalized at Osaka University Hospital between November 2010 and December 2011. BMI and glycated hemoglobin (HbA1c) were examined on admission, at discharge and at 1, 3, and 6 months after discharge. For the liraglutide group (BMI; 31.3 +/- 5.3 kg/m2, n = 29), patients were introduced to liraglutide after correction of hyperglycemic by insulin or oral glucose-lowering drugs and maintained on liraglutide after discharge. Eating behavior was assessed in patients treated with liraglutide using The Guideline For Obesity questionnaire issued by the Japan Society for the Study of Obesity, at admission, discharge, 3 and 6 months after discharge. For the insulin group (BMI; 29.1 +/- 3.0 kg/m2, n = 28), each patient was treated with insulin during hospitalization and glycemic control maintained by insulin after discharge. RESULTS: Liraglutide induced significant and persistent weight loss from admission up to 6 months after discharge, while no change in body weight after discharge was noted in the insulin group. Liraglutide produced significant improvements in all major scores of eating behavior questionnaire items and such effect was maintained at 6 months after discharge. Weight loss correlated significantly with the decrease in scores for recognition of weight and constitution, sense of hunger, and eating style. CONCLUSION: Liraglutide produced meaningful long-term weight loss and significantly improved eating behavior in obese Japanese patients with type 2 diabetes.     

Achieving further glycemic control in type 2 diabetes mellitus

Objectives To identify patients with type 2 diabetes mellitus who were in poor glycemic control and therapeutic adjustments that might improve control. Design Using electronic pharmacy data, we assigned subjects to 1 of 4 therapeutic categories. We then identified patients within each category who did not meet the recommended standard of glycemic control (glycosylated hemoglobin [Hb A_1c] <0.08 [<8.0%]) and studied their therapetic regimens for possible improvements. Subjects The subjects were 5,061 members of a large group-model health maintenance organization who had type 2 diabetes and 12 months of 1997 health plan eligibility. Main outcome measures The dosage of antihyperglycemic agents (sulfonylureas, metformin, and insulin) in relation to glycemic control as measured by the Hb A_1c. Results A significant number (n = 1,570 [31.0%]) of persons with type 2 diabetes might improve their glycemic control with simple adjustments to their pharmacologic therapy. Conclusion Busy clinicians with heavy workloads can improve their management of diabetes by identifying patients whose glycemic control could be improved through a change in medication or simple adjustment in dosage.     

Effect of insulin therapy on plasma leptin and body weight in patients with type 2 diabetes.

AIMS: This study set out to define relationships between changes in plasma leptin and changes in body weight, plasma insulin and blood glucose control during a 12-month crossover study of once-daily Ultratard or twice-daily Insulatard insulin. PATIENTS AND METHODS: Fasting plasma leptin and insulin were measured during a multicentre cross-over study involving 60 subjects with type 2 diabetes (fasting glucose > 8 mM). After a 2-month run-in, there were two 6-month periods of treatment with Insulatard or Ultratard insulin. RESULTS: Mean plasma leptin increased significantly in both groups after insulin therapy was instigated (12.8 +/- 8.1 to 22.9 +/- 13.1 ng/ml in the Insulatard group; 12.1 +/- 7.2 to 19.2 +/- 12.3 ng/ml in the Ultratard group). Weight also increased significantly in both groups (82.4 +/- 14.3 kg to 88.8 +/- 14.3 kg and 82.2 +/- 15.3 kg to 85.3 +/- 15.2 kg respectively). The increase in plasma leptin correlated well with the increase in weight (R = 0.416, p = 0.001), and this correlation continued after the crossover point. Plasma leptin correlated with BMI throughout the study (R = 0.540, p = 0.000). CONCLUSION: The sustained rise in body weight despite a substantial increase in plasma leptin suggests that either resistance to the hypothalamic action of leptin develops when insulin therapy is begun in type 2 diabetes, or that resetting of the set point for body weight occurs such that a larger body mass is tolerated for a given level of plasma leptin.     

Beneficial effects of oral chromium picolinate supplementation on glycemic control in patients with type 2 diabetes: A randomized clinical study

BackgroundChromium is an essential mineral that contributes to normal glucose function and lipid metabolism. This study evaluated the effect of chromium picolinate (CrPic) supplementation in patients with type 2 diabetes mellitus (T2DM).MethodsA four month controlled, single blind, randomized trial was performed with 71 patients with poorly controlled (hemoglobin A1c [HbA1c] > 7%) T2DM divided into 2 groups: Control (n = 39, using placebo), and supplemented (n = 32, using 600 μg/day CrPic). All patients received nutritional guidance according to the American Diabetes Association (ADA), and kept using prescribed medications. Fasting and postprandial glucose, HbA1c, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides and serum ferritin were evaluated.ResultsCrPic supplementation significantly reduced the fasting glucose concentration (−31.0 mg/dL supplemented group; −14.0 mg/dL control group; p < 0.05, post- vs. pre-treatment, in each group) and postprandial glucose concentration (−37.0 mg/dL in the supplemented group; −11.5 mg/dL in the control group; p < 0.05). HbA1c values were also significantly reduced in both groups (p < 0.001, comparing post- vs. pre-treatment groups). Post-treatment HbA1c values in supplemented patients were significantly lower than those of control patients. HbA1c lowering in the supplemented group (−1.90), and in the control group (−1.00), was also significant, comparing pre- and post-treatment values, for each group (p < 0.001 and p < 0.05, respectively). CrPic increased serum chromium concentrations (p < 0.001), when comparing the supplemented group before and after supplementation. No significant difference in lipid profile was observed in the supplemented group; however, total cholesterol, HDL-c and LDL-c were significantly lowered, comparing pre- and post-treatment period, in the control group (p < 0.05).ConclusionsCrPic supplementation had a beneficial effect on glycemic control in patients with poorly controlled T2DM, without affecting the lipid profile. Additional studies are necessary to investigate the effect of long-term CrPic supplementation.     

Relation between psychosocial variables and the glycemic control of patients with type 2 diabetes: A cross-sectional and prospective study

Background  

This cross-sectional and prospective study used a variety of psychological inventories to evaluate the relationship between psychosocial factors and the glycemic control of patients with type 2 diabetes.     

Asymmetric dimethylarginine and long-term adverse cardiovascular events in patients with type 2 diabetes: relation with the glycemic control

Patients with type 2 diabetes are at a high risk for acute cardiovascular events, which usually arise from the rupture of a vulnerable coronary lesion characterized by specific morphological plaque features. Thus, the identification of vulnerable plaques is of utmost clinical importance in patients with type 2 diabetes. However, there is currently no scoring system available to identify vulnerable lesions based on plaque characteristics. Thus, we aimed to characterize the diagnostic value of optical coherence tomography (OCT) - derived lesion characteristics to quantify plaque vulnerability both as individual parameters and when combined to a score in patients with type 2 diabetes. OCT was performed in the coronary culprit lesions of 112 patients with type 2 diabetes. The score, which quantifies plaque vulnerability, was defined as the predicted probability that a lesion is the cause for an acute coronary syndrome (ACS) (vs. stable angina (SAP)) based on its specific plaque morphology. Multivariable logistic regression analysis demonstrated that plaque vulnerability was independently predicted by the minimal fibrous cap thickness overlying a lesion’s lipid core (odds ratio (OR) per 10 μm 0.478, p = 0.002), the medium lipid arc (OR per 90° 13.997, p < 0.001), the presence of macrophages (OR 4.797, p = 0.015) and the lipid plaque length (OR 1.290, p = 0.098). Receiver-operating-characteristics (ROC) analyses demonstrated that these parameters combined to a score demonstrate an excellent diagnostic efficiency to identify culprit lesions of patients with ACS (vs. SAP, AUC 0.90, 95% CI 0.84-0.96). This is the first study to present a score to quantify lesion vulnerability in patients with type 2 diabetes. This score may be a valuable adjunct in decision-making and useful in guiding coronary interventions.     

Effects of glycemic control on target organ responses to epinephrine in type 1 diabetes

Severe hypoglycemia occurs in intensively treated patients with type 1 diabetes mellitus (T1DM) due in part to deficient epinephrine counterregulatory responses. Previously, we have found that T1DM patients demonstrated a spectrum of altered responses to epinephrine at a variety of target organs compared with nondiabetic healthy subjects. What is not known is whether intensive glycemic control further modifies target organ responses in individuals with T1DM. Therefore, the aim of this study is to assess whether there is tissue specific (liver, muscle, adipose tissue, pancreas and cardiovascular) resistance to epinephrine in intensively controlled (IC) T1DM compared with those with conventional control (CC). Eight IC patients (age 33 +/- 4 yr, BMI 24 +/- 2 kg/m2, Hb A1C 6.7 +/- 0.1%), and 11 CC patients (age 35 +/- 3 yr, BMI 25 +/- 1 kg/m2, Hb A1C 9.6 +/- 0.1%) underwent two separate randomized, single-blind, 2-h hyperinsulinemic euglycemic clamp studies with (EPI) and without (NO EPI) epinephrine infusion. Epinephrine levels during EPI were similar in all groups (5,197 +/- 344 pmol/l). Glucose (5.3 +/- 0.1 mmol/l) and insulin levels (515 +/- 44 pmol/l) were similar in all groups during the glucose clamps. Endogenous glucose production (EGP) and glucose uptake (R(d)) were determined using [3-H3]glucose. Muscle biopsy was performed at the end of each study. IC had a significantly reduced EGP and R(d) responses to EPI compared with CC. Glucagon responses to EPI were similarly blunted in both IC and CC. Free fatty acid and glycerol response to EPI was greater in CC compared with IC. There was a significantly greater systolic blood pressure response to EPI in CC. We conclude that, despite similar epinephrine, insulin, and glucose levels, intensively treated T1DM patients had reduced cardiovascular, skeletal muscle, hepatic, and adipose target organ responses to EPI compared with conventionally treated T1DM patients.     

Genetic variability in sodium-glucose cotransporter 2 influences glycemic control and risk for diabetic retinopathy in type 2 diabetes patients

BackgroundGluconeogenesis and renal glucose excretion in kidneys both play an important role in glucose homeostasis. Sodium-glucose cotransporter (SGLT2), coded by the SLC5A2 gene is responsible for reabsorption up to 99% of the filtered glucose in proximal tubules. SLC5A2 genetic polymorphisms were suggested to influence glucose homeostasis. We investigated if common SLC5A2 rs9934336 polymorphism influences glycemic control and risk for macro or microvascular complications in Slovenian type 2 diabetes (T2D) patients.MethodsAll 181 clinically well characterized T2D patients were genotyped for SLC5A2 rs9934336 G>A polymorphism. Associations with glycemic control and T2D complications were assessed with nonparametric tests and logistic regression.ResultsSLC5A2 rs9934336 was significantly associated with increased fasting blood glucose levels (P<0.001) and HbA1c levels under the dominant genetic model (P=0.030). After adjustment for T2D duration, significantly higher risk for diabetic retinopathy was present in carriers of at least one polymorphic SLC5A2 rs9934336 A allele compared to non-carriers (OR=7.62; 95%CI=1.65-35.28; P=0.009).ConclusionsOur pilot study suggests an important role of SLC5A2 polymorphisms in the physiologic process of glucose reabsorption in kidneys in T2D patients. This is also the first report on the association between SLC5A2 polymorphism and diabetic retinopathy.     

Moderate weight loss improves heart rate variability in overweight and obese adults with type 2 diabetes

The objective of this study was to determine the effects of weight loss on heart rate variability (HRV) and its association with traditional cardiovascular disease risk factors in overweight and obese patients with type 2 diabetes. Forty five patients [body mass index (BMI) 35.4 ± 0.7 kg/m2; age 56.5 ± 1.1 yr] with type 2 diabetes followed an energy-restricted diet (6-7 MJ/day) for 16 wk. Body weight, blood pressure, glucose, insulin, insulin resistance [homeostasis model assessment index 2 (HOMA2)], glycosylated hemoglobin (HbA1c), total cholesterol, low-density lipoproteins (LDL), high-density lipoproteins (HDL), triglycerides, resting HR, and HRV were measured before and after the intervention period. Mean reduction in body weight was 11.1 ± 1.0 kg (10%), with significant reductions in blood pressure (-10%), total cholesterol (-15.9%), LDL (-17.7%), HDL (-7.5%), triglycerides (-21.2%), glucose (-23.4%), insulin (-37.6%), HOMA2 (-40.1%), and HbA1c (-14.5%) (P ≤ 0.05 for all variables). There were increases in several HRV components, including total power (1,370 ± 280 to 2,045 ± 280 ms2), low-frequency power (345 ± 70 to 600 ± 108 ms2), SD of normal to normal intervals (SDNN; 35.0 ± 2.5 to 43.0 ± 2.7 s), and square root of the mean squared differences of successive normal to normal intervals (RMSSD; 23.0 ± 3.5 to 32.0 ± 3.1 s), and a decrease in HR (69.0 ± 1.3 to 60.0 ± 1.2 beats/min) (P ≤ 0.03 for all variables). Changes in HR, SDNN, total power, and low-frequency power correlated with change in BMI (P < 0.05). In addition to improvements in traditional cardiovascular and metabolic risk factors, weight loss improves HRV in overweight and obese patients with type 2 diabetes.     

ADIPOQ,KCNJ11 and TCF7L2 polymorphisms in type 2 diabetes in Kyrgyz population: A case‐control study

The aim of this study was to ascertain the polymorphic markers profile of ADIPOQ, KCNJ11 and TCF7L2 genes in Kyrgyz population and to analyze the association of polymorphic markers and combinations of ADIPOQ gene's G276T locus, KCNJ11 gene's Glu23Lys locus and TCF7L2 gene's VS3C>T locus with type two diabetes (T2D) in Kyrgyz population. In this case‐control study, 114 T2D patients 109 non‐diabetic participants were genotyped using polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP). Two individual polymorphisms (ADIPOQ rs1501299, KCNJ11 rs5219) were found to be associated with T2D. We found two (Lys23Lys/CC and Glu23Lys/CT) of the overall nine combinations, which were more prevalent in T2D group compared to controls (χ² = 4.21, P = 0.04). Lys23Lys/CC combination was associated with a 2.65‐fold increased likelihood of T2D (OR = 2.65, 95% CI 1.12‐6.28), whereas the Glu23Lys/CT combination also increased such likelihood (OR = 3.88, 95% CI 1.27‐11.91). This study demonstrated some association of 276T allele and ADIPOQ gene G276T heterozygous genotype as well as KCNJ11 gene 23Lys allele with T2D in ethnic Kyrgyz, but study results should be interpreted with caution because of the limited statistical power.     

益生菌对老年2型糖尿病患者的影响

目的探讨益生菌对老年2型糖尿病患者肠道菌群、肠道屏障功能及糖脂代谢水平的影响。方法选取2017年10月至2019年10月我院收治的200例2型糖尿病患者为研究对象。入选患者随机分为观察组和对照组,各100例。比较两组患者治疗前后肠道菌群变化情况,血清二胺氧化酶(DAO)、内毒素(ET)、D 乳酸(D lac)、糖化血红蛋白(HbA_1c)、空腹血糖(FPG)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL C)、高密度脂蛋白胆固醇(HDL C)水平。记录两组患者治疗过程中不良反应发生情况。结果治疗前,两组患者肠道双歧杆菌、乳杆菌、拟杆菌、肠球菌、肠杆菌及酵母菌数量比较差异无统计学意义(均P>0.05);治疗后,两组患者肠道双歧杆菌、乳杆菌、拟杆菌数量均显著增加,而肠球菌、肠杆菌及酵母菌数量显著降低,同时观察组患者变化幅度大于对照组(均P<0.05)。治疗前,两组患者血清DAO、ET、D lac、HbA_1c、FPG、TC、TG、LDL C、HDL C水平比较差异无统计学意义(均P>0.05)。治疗后,两组患者血清DAO、ET、D lac、HbA_1c、FPG、TC、TG、LDL C、HDL C水平均显著降低(P<0.05),同时观察组上述指标水平低于对照组(P<0.05)。观察组患者治疗过程中不良反应总发生率为9.0%,对照组为7.0%,两组比较差异无统计学意义(χ²=0.272,P=0.602)。结论益生菌可有效调节老年2型糖尿病患者肠道菌群,提高肠道屏障功能,控制糖脂代谢水平,安全性较高,具有较好的辅助治疗作用。     

The effects of the dietary glycemic load on type 2 diabetes risk factors during weight loss

Objective: To compare the effects of two calorie-restricted diets that differ in glycemic load (GL) on glucose tolerance and inflammation. Research Methods and Procedures: Thirty-four healthy overweight adults, ages 24 to 42 years, were randomized to 30% provided calorie-restricted diets with high (HG) or low (LG) glycemic load for 6 months. Outcomes were changes in glucose-insulin dynamics and C-reactive protein (CRP) levels. Results: Compared with baseline, levels of fasting insulin, homeostasis model assessment of insulin resistance, post-load insulin at 30 minutes, and incremental area-under-the-curve-insulin during the oral glucose tolerance test were significantly lower in both groups at 6 months (p range, 0.01 to 0.05), but after adjustment for baseline values and weight change, there were no differences between the two groups with regard to changes over time in any parameter. The mean percentage change in insulin sensitivity by a frequently sampled intravenous glucose tolerance test was +26% in the HG group and +24% in the LG group (p = 0.83); first-phase acute insulin release was −20% in the HG group and −21% in the LG group (p = 0.77). More participants on the LG diet (14 of 16 subjects) had a decline in serum CRP, compared with those on the HG diet (7 of 16 subjects) (p < 0.05). Discussion: In healthy overweight adults provided with food for 6 months, the dietary GL did not seem to influence chronic adaptations in glucose-insulin dynamics above that associated with weight loss. This finding highlights the importance of absolute weight loss over the dietary macronutrient composition used to achieve weight loss. The finding of greater declines in CRP concentration after consumption of a low-GL diet warrants further investigation.     

Effects of bilateral auricular acupuncture stimulation on body weight in healthy volunteers and mildly obese patients

We investigated the effects of auricular acupuncture stimulation on non-obese healthy volunteers and mildly obese patients. Subjects (n = 55 and 5, respectively) averaged 34.5 years old, and BMI was 24.3 and less than 27.5 kg/m2, respectively. We also studied the effects of single-blind sham treatment in approximately 500 age-, sex-, and BMI-matched subjects. Small (0.15 x 2.0 mm) auricular needles were placed intracutaneously into the bilateral cavum conchae identified by having a resistance of less than 100 kOmega/cm2. In the 2-week pretreatment the period, in which body weight was measured without auricular acupuncture stimulation, 57.1% of the subjects showed a reduction in body weight. This indicates that charting one's own body weight might itself be a useful method of weight control. In the auricular acupuncture treatment period, 35 healthy subjects of 55 (63.6%) showed a decreased body weight, 11 (20%) showed an increased body weight, and 9 (16.4%) showed no change in body weight. The obese patients showed individual variation, but all achieved weight reduction, with a highly significant correlation between body weight and fat volume. The CT/MRI cross-sectional pictures supported these findings. Sham treatment had no statistically significant effect on body weight. These results suggest that success in achieving weight reduction can be partly attributed to the act of charting of one's own weight pattern. Bilateral auricular acupuncture stimulation can help reduce body weight both in mildly obese patients and in healthy non-obese subjects. In conclusion, this is in accord with the bilateral auricular acupuncture stimulation that it may be useful in the treatment of the obesity. We propose a possible mechanism for the weight-reducing effects of bilateral auricular acupuncture stimulation.     

One-year changes in symptoms of depression and weight in overweight/obese individuals with type 2 diabetes in the Look AHEAD study

Depressed individuals are frequently excluded from weight loss trials because of fears that weight reduction may precipitate mood disorders, as well as concerns that depressed participants will not lose weight satisfactorily. The present study examined participants in the Look AHEAD study to determine whether moderate weight loss would be associated with incident symptoms of depression and suicidal ideation, and whether symptoms of depression at baseline would limit weight loss at 1 year. Overweight/obese adults with type 2 diabetes (n = 5,145) were randomly assigned to an Intensive Lifestyle Intervention (ILI) or a usual care group, Diabetes Support and Education (DSE). Of these, 5,129 participants completed the Beck Depression Inventory (BDI) and had their weight measured at baseline and 1 year. Potentially significant symptoms of depression were defined by a BDI score ≥10. Participants in ILI lost 8.6 ± 6.9% of initial weight at 1 year, compared to 0.7 ± 4.8% for DSE (P < 0.001, effect size = 1.33), and had a reduction of 1.4 ± 4.7 points on the BDI, compared to 0.4 ± 4.5 for DSE (P < 0.001, effect size = 0.23). At 1 year, the incidence of potentially significant symptoms of depression was significantly lower in the ILI than DSE group (6.3% vs. 9.6%) (relative risk (RR) = 0.66, 95% confidence interval (CI) = 0.5, 0.8; P < 0.001). In the ILI group, participants with and without symptoms of depression lost 7.8 ± 6.7% and 8.7 ± 6.9%, respectively, a difference not considered clinically meaningful. Intentional weight loss was not associated with the precipitation of symptoms of depression, but instead appeared to protect against this occurrence. Mild (or greater) symptoms of depression at baseline did not prevent overweight/obese individuals with type 2 diabetes from achieving significant weight loss.     

Heme oxygenase microsatellite polymorphism, oxidative stress, glycemic control, and complication development in type 2 diabetes patients

Heme oxygenase-1 (HMOX-1) is activated by oxidative stress, and gene responsiveness is reportedly determined by the number of dinucleotide (GT(n)) repeats in its highly polymorphic promoter region. "Short" (S; GT(n)<25) alleles reportedly associate with higher response, lower oxidative stress, lower risk of type 2 diabetes mellitus (type 2DM), and better glycemic control and outcome, but data are conflicting. We investigated GT(n) in type 2DM subjects (all ethnic Chinese) in relation to basal glycemic control, oxidative stress, and outcome during up to 9 years' follow-up. Fasting blood from 418 type 2 DM subjects was collected at entry for GT(n) genotyping, glycated hemoglobin, glucose, lipids, and biomarkers of oxidative stress and antioxidants. A subset (n=368) was followed for up to 9 years for incident complications or death. GT(n) genotype distribution was 128, 182, and 108 for, respectively, S/S, S/L, and L/L. No significant differences in glycemic control, lipids, or oxidative stress were seen across genotypes. During follow-up, 168/368 subjects developed complications. No association was seen with GT(n). No difference in plasma HO-1 was seen between genotypes in a small substudy (S/S n=21 vs L/L n=23). Glycated hemoglobin and lymphocytic DNA damage was higher (p<0.05) at entry in the incident complications group. No other significant differences were seen in oxidative stress or antioxidants. Data do not support the postulated link between HMOX-1 microsatellite polymorphism and type 2 DM or the putative beneficial effect of the S allele on glycemic control, oxidative stress, or outcome in type 2 DM patients, at least in this particular population.