Prevention of type 2 diabetes with troglitazone in the Diabetes Prevention Program

The Diabetes Prevention Program (DPP) was a randomized clinical trial of prevention of type 2 diabetes in high-risk people. Troglitazone, an insulin-sensitizing agent, was used initially but was discontinued during the trial. Troglitazone therapy was compared with other DPP interventions, considering both the short-term "in-trial" results and the longer-term results after troglitazone were discontinued. From 1996 to 1998, participants were randomly assigned to treatment with metformin (n = 587), troglitazone (n = 585), double placebo (n = 582), or intensive lifestyle intervention (ILS) (n = 589). Because of concern regarding its liver toxicity, the troglitazone arm was discontinued in June 1998, after which follow-up of all participants continued. During the mean 0.9 year (range 0.5-1.5 years) of troglitazone treatment, the diabetes incidence rate was 3.0 cases/100 person-years, compared with 12.0, 6.7, and 5.1 cases/100 person-years in the placebo, metformin, and ILS participants (P < 0.001, troglitazone vs. placebo; P = 0.02, troglitazone vs. metformin; P = 0.18, troglitazone vs. ILS). This effect of troglitazone was in part due to improved insulin sensitivity with maintenance of insulin secretion. During the 3 years after troglitazone withdrawal, the diabetes incidence rate was almost identical to that of the placebo group. Troglitazone, therefore, markedly reduced the incidence of diabetes during its limited period of use, but this action did not persist. Whether other thiazolidinedione drugs used for longer periods can safely prevent diabetes remains to be determined.     

Mechanism of metformin action in non-insulin-dependent diabetes

The mechanism of action of metformin was studied by comparing glucose turnover before and after a 75-g oral glucose load in 10 nonobese men with non-insulin-dependent diabetes mellitus (NIDDM) during metformin and placebo therapy by the combined application of the forearm and double-isotope techniques. During the study, 9 of the 10 patients were regularly receiving glibenclamide therapy. In 5 of the men, the first study was performed during metformin therapy, and the second study was done during placebo administration; in the other 5 subjects, the order was reversed. The interval between the studies was at least 3 mo. The metformin dosage was 1 g twice daily in 9 of the patients and 850 mg thrice daily in the 10th subject. In the basal state, metformin administration reduced plasma glucose levels from 172 +/- 14 to 103 +/- 9 mg/dl (P less than .005), hepatic glucose output (HGO) from 2.67 +/- 0.15 to 2.20 +/- 0.20 mg X kg-1 X min-1 (P less than .02), and forearm glucose uptake (FGU) from 0.106 +/- 0.18 to 0.039 +/- 0.016 mg X 100 ml-1 forearm X min-1 (P less than .005), whereas insulin (23 +/- 6 microU/ml) and lactate (1.56 +/- 0.18 mM) levels were unchanged. Although the oral glucose tolerance curve (OGTC) was significantly lowered by metformin, the incremental area under the curve and the insulin response were unchanged. The systemic appearance of ingested glucose was unaffected by metformin; 64 +/- 2% of the load was recovered peripherally in 3 h.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanism by which metformin reduces glucose production in type 2 diabetes

To examine the mechanism by which metformin lowers endogenous glucose production in type 2 diabetic patients, we studied seven type 2 diabetic subjects, with fasting hyperglycemia (15.5 +/- 1.3 mmol/l), before and after 3 months of metformin treatment. Seven healthy subjects, matched for sex, age, and BMI, served as control subjects. Rates of net hepatic glycogenolysis, estimated by 13C nuclear magnetic resonance spectroscopy, were combined with estimates of contributions to glucose production of gluconeogenesis and glycogenolysis, measured by labeling of blood glucose by 2H from ingested 2H2O. Glucose production was measured using [6,6-2H2]glucose. The rate of glucose production was twice as high in the diabetic subjects as in control subjects (0.70 +/- 0.05 vs. 0.36 +/- 0.03 mmol x m(-2) min(-1), P < 0.0001). Metformin reduced that rate by 24% (to 0.53 +/- 0.03 mmol x m(-2) x min(-1), P = 0.0009) and fasting plasma glucose concentration by 30% (to 10.8 +/- 0.9 mmol/l, P = 0.0002). The rate of gluconeogenesis was three times higher in the diabetic subjects than in the control subjects (0.59 +/- 0.03 vs. 0.18 +/- 0.03 mmol x m(-2) min(-1) and metformin reduced that rate by 36% (to 0.38 +/- 0.03 mmol x m(-2) x min(-1), P = 0.01). By the 2H2O method, there was a twofold increase in rates of gluconeogenesis in diabetic subjects (0.42 +/- 0.04 mmol m(-2) x min(-1), which decreased by 33% after metformin treatment (0.28 +/- 0.03 mmol x m(-2) x min(-1), P = 0.0002). There was no glycogen cycling in the control subjects, but in the diabetic subjects, glycogen cycling contributed to 25% of glucose production and explains the differences between the two methods used. In conclusion, patients with poorly controlled type 2 diabetes have increased rates of endogenous glucose production, which can be attributed to increased rates of gluconeogenesis. Metformin lowered the rate of glucose production in these patients through a reduction in gluconeogenesis.     

Mechanism of immune attack in the progression of obesity-related type 2 diabetes

Obesity and overweight are widespread issues in adults, children, and adolescents globally, and have caused a noticeable rise in obesity-related complications such as type 2 diabetes mellitus (T2DM). Chronic low-grade inflammation is an important promotor of the pathogenesis of obesity-related T2DM. This proinflammatory activation occurs in multiple organs and tissues. Immune cell-mediated systemic attack is considered to contribute strongly to impaired insulin secretion, insulin resistance, and other metabolic disorders. This review focused on highlighting recent advances and underlying mechanisms of immune cell infiltration and inflammatory responses in the gut, islet, and insulin-targeting organs (adipose tissue, liver, skeletal muscle) in obesity-related T2DM. There is current evidence that both the innate and adaptive immune systems contribute to the development of obesity and T2DM.     

减重手术治疗2型糖尿病机制研究进展

2型糖尿病患者接受减重手术后糖尿病症状显著缓解并能长期维持,主要是因为术后胃肠道激素的改变,此外体质量下降、饮食减少以及其他的因素也起着一定作用。随着其治疗机制研究的不断深入,减重手术有望成为治疗2型糖尿病的一种主要手段。     

两种手术方式治疗2型糖尿病机制的研究

Objective To clarify mechanism of Roux-en-Y gastric bypass (RYGB) and gastric banding on diabetes induced by STZ injection. Methods 40 rats with STZ induced diabetes were randomly allocated into Roux-en-Y gastric bypass (RYGB) group (group RYGB, n=10), gastric banding group (group GB, n=10 ), diet control group (group F, n=10), control group (group C,n= 10). The fasting blood glucose, the fasting insulin IGF-1, the fasting Plasma leptin, the fasting plasma insulin level, the weight and the food-intake, the operation time, the death rate were measured and recored before and after operation on 1st , 2nd, 3 rd ,4th, 8th and 16 th week postoperatively. Results The fasting blood glucose of the group of gastric banding(GB) descended to (12.6±3.7) mmol/L, the fasting plasma insulin rose to (58.7±9.2) mIU/L, the fasting plasma leptin descended to (14.6±3.3) pg/ml, the weight was (212.6±15.1) g.There were significant differences between before and after operation on 16 th week(P<0.01). The fasting blood glucose of the group of Roux-en-Y (RYBG) descended to 8.8±4.9 mmol/L in the sixteenth week, the fasting insulin IGF-1 rose to (148.6±7.3) ng/L, the fasting plasma insulin rose to (14.1±3.5) pg/ml, the fasting plasma leptin descended to 14.1±3.5 pg/ml, the weight was (200±15.1) g. There were significant differences between before and after operation 16 th week (P<0.01). There were significant differences of the fasting plasma insulin and the the fasting plasma leptin between group F and group C during the 3 rd to 4th week after operation (P<0.05). Compared the weight of the group F and the group C on the third week of operation, there were significant differences (P<0.05), and there were no significant differences in other time. The fasting blood glucose of the group F and the group C had no sig-nificant differences between before and after operation.(P<0.05). Conclusions The fasting blood glucose and the fasting insulin level of the group F improve more than of the group GB at the same time. The plasma insulin and the plasma leptin of the two groups all work in glucose control. The diet control and the modification of the plasma insulin and the plasma leptin all play a major role in the gastric banding mechanism, and the IGF-1 may work in the descending the blood glucose after the operation of Roux-en-Y. In the operation time and die rate, the group of F surpass the group of GB.     

两种手术方式治疗2型糖尿病机制的研究

Objective To clarify mechanism of Roux-en-Y gastric bypass (RYGB) and gastric banding on diabetes induced by STZ injection. Methods 40 rats with STZ induced diabetes were randomly allocated into Roux-en-Y gastric bypass (RYGB) group (group RYGB, n=10), gastric banding group (group GB, n=10 ), diet control group (group F, n=10), control group (group C,n= 10). The fasting blood glucose, the fasting insulin IGF-1, the fasting Plasma leptin, the fasting plasma insulin level, the weight and the food-intake, the operation time, the death rate were measured and recored before and after operation on 1st , 2nd, 3 rd ,4th, 8th and 16 th week postoperatively. Results The fasting blood glucose of the group of gastric banding(GB) descended to (12.6±3.7) mmol/L, the fasting plasma insulin rose to (58.7±9.2) mIU/L, the fasting plasma leptin descended to (14.6±3.3) pg/ml, the weight was (212.6±15.1) g.There were significant differences between before and after operation on 16 th week(P<0.01). The fasting blood glucose of the group of Roux-en-Y (RYBG) descended to 8.8±4.9 mmol/L in the sixteenth week, the fasting insulin IGF-1 rose to (148.6±7.3) ng/L, the fasting plasma insulin rose to (14.1±3.5) pg/ml, the fasting plasma leptin descended to 14.1±3.5 pg/ml, the weight was (200±15.1) g. There were significant differences between before and after operation 16 th week (P<0.01). There were significant differences of the fasting plasma insulin and the the fasting plasma leptin between group F and group C during the 3 rd to 4th week after operation (P<0.05). Compared the weight of the group F and the group C on the third week of operation, there were significant differences (P<0.05), and there were no significant differences in other time. The fasting blood glucose of the group F and the group C had no sig-nificant differences between before and after operation.(P<0.05). Conclusions The fasting blood glucose and the fasting insulin level of the group F improve more than of the group GB at the same time. The plasma insulin and the plasma leptin of the two groups all work in glucose control. The diet control and the modification of the plasma insulin and the plasma leptin all play a major role in the gastric banding mechanism, and the IGF-1 may work in the descending the blood glucose after the operation of Roux-en-Y. In the operation time and die rate, the group of F surpass the group of GB.     

Effects of troglitazone on blood concentrations of plasminogen activator inhibitor 1 in patients with type 2 diabetes and in lean and obese normal subjects

Low plasma fibrinolytic activity in association with increased plasma plasminogen activator inhibitor 1 (PAI-1) levels has been linked to an increased risk of atherosclerosis in obesity and type 2 diabetes. We tested the hypothesis that troglitazone, which improves insulin sensitivity and lowers plasma insulin levels in insulin-resistant obese subjects and patients with type 2 diabetes, would also lower circulating PAI-1 antigen concentrations and activity. We assessed insulin sensitivity (5-h, 80 mU x m(-2) x min(-1) hyperinsulinemic-euglycemic clamp) and measured plasma PAI-1 antigen and activities and tissue plasminogen activator (tPA) in 14 patients with type 2 diabetes and 20 normal control subjects (10 lean, 10 obese) before and after 3 months of treatment with troglitazone (600 mg/day). At baseline, plasma PAI-1 antigen levels after an overnight fast were significantly higher in the obese (33.5 +/- 4.7 microg/l) and type 2 diabetic subjects (54.9 +/- 6.3 microg/l) than in the lean control subjects (16.3 +/- 3.2 microg/l; P < 0.01 and P < 0.001, respectively). Troglitazone decreased plasma PAI-1 antigen concentrations in the diabetic patients (36.8 +/- 5.0 microg/l; P < 0.001 vs. baseline), but the reduction in the obese subjects did not reach statistical significance (baseline, 33.5 +/- 4.7; after troglitazone, 25.6 +/- 5.2 microg/l). Changes in plasma PAI-1 activity paralleled those of PAI-1 antigen. The extent of the reduction in plasma PAI-1 antigen concentrations in the diabetic patients after troglitazone correlated with the reductions in fasting plasma insulin (r = 0.60, P < 0.05), nonesterified fatty acid (r = 0.63, P < 0.02), and glucose concentrations (r = 0.64, P < 0.02) but not with the improvement in glucose disposal rates during the glucose clamps. Three nonresponders to troglitazone with respect to effects on insulin sensitivity and fasting glucose and insulin levels also had no reduction in circulating PAI-1. In conclusion, troglitazone enhances fibrinolytic system activity in insulin-resistant type 2 diabetic patients. This effect appears to be intimately linked to its potential to lower plasma insulin levels and improve glycemic control through its peripheral tissue insulin-sensitizing effects.     

Characteristics of autoimmunity in type 1 diabetes and type 1.5 overlap with type 2 diabetes

This presentation is an overview of mechanisms for developing and maintaining self-tolerance in mammalian organisms. Because this meeting is focused on type 1 diabetes and its mechanisms, the discussion deals primarily with mechanisms of T-cell tolerance, since type 1 diabetes in both effector and initiator phases is primarily a T-cell-mediated autoimmune disease. Emphasis is placed on more recently discovered mechanisms of maintaining self-tolerance (autoimmune regulator [AIRE]) and a new defect in T-cell negative selection. The emerging picture is that of a polygenic disease with various combinations of different alleles of many genes with important roles in the normal immune response or normal immune responses.     

Biphasic vasodilator action of troglitazone on the renal microcirculation.

Recent studies have demonstrated that thiazolidinediones, novel antidiabetic compounds that improve the insulin sensitivity, lower BP and decrease urinary protein excretion. However, neither the target vasculature nor the underlying mechanism for their actions is well understood. In this study, the action of troglitazone (Tro), a thiazolidinedione compound, on the glomerular afferent (Af-Arts) and efferent (Ef-Arts) arterioles, crucial vascular segments to the control of glomerular hemodynamics, were directly examined. Rabbit Af-Arts or Ef-Arts were microdissected from the superficial cortex and perfused at constant pressure. Increasing doses of Tro (10(-8) to 10(-5) M) were added to both the bath and lumen of preconstricted arterioles. In Af-Arts, Tro caused dose-dependent and biphasic dilation. Tro at 10(-5) M increased the diameter by 28 +/- 6% (n = 8, P < 0.01) until 20 min, with the diameter remaining at this level for 60 min, and then Tro began to dilate Af-Arts again. At 120 min, Tro at 10(-5) M further increased the diameter by 23 +/- 4% (n = 6). Disrupting the endothelium had no effect on either dilation (n = 7 or n = 5). Pretreatment with SKF 96365 (50 microM), which inhibits both voltage- and receptor-operated calcium channels, abolished the early-phase dilation without affecting the late-phase dilation; 20 or 120 min after adding Tro at 10(-5) M, the diameter increased by 4 +/- 2% (n = 7) or 28 +/- 3% (n = 6), respectively. In contrast to Af-Arts, Tro caused monophasic dilation in Ef-Arts; Tro at 10(-5) M did not cause significant dilation until 80 min, and at 120 min the diameter increased by 37 +/- 4% (n = 5). These results suggest that in the Af-Art Tro has biphasic endothelium-independent vasodilator action, which is partly mediated by an inhibition of calcium influx. This vasodilator action may play a role in the BP-lowering effect of Tro. In addition, by dilating the postglomerular Ef-Art, Tro may decrease the glomerular capillary pressure and hence the excretion of urinary protein.     

Genetics of type 2 diabetes

Type 2 diabetes (T2D) is the result of interaction between environmental factors and a strong hereditary component. We review the heritability of T2D as well as the history of genetic and genomic research in this area. Very few T2D risk genes were identified using candidate gene and linkage-based studies, but the advent of genome-wide association studies has led to the identification of multiple genes, including several that were not previously known to play any role in T2D. Highly replicated genes, for example TCF7L2, KCNQ1 and KCNJ11, are discussed in greater detail. Taken together, the genetic loci discovered to date explain only a small proportion of the observed heritability. We discuss possible explanations for this “missing heritability”, including the role of rare variants, gene-environment interactions and epigenetics. The clinical utility of current findings and avenues of future research are also discussed.     

Muscle strength in type 2 diabetes

Motor function in type 2 diabetes is largely unknown. In 36 type 2 diabetic patients and in 36 control subjects matched for sex, age, weight, height, and physical activity, strength of flexors and extensors at elbow, wrist, knee, and ankle was assessed at isokinetic dynamometry. The degree of neuropathy was determined by clinical scores, nerve conduction studies, and quantitative sensory testing. Eventually, all results were summed to obtain a neuropathy rank-sum score (NRSS). The degree of nephropathy and retinal condition were also evaluated. Diabetic patients had a 17 and 14% reduction of strength of ankle flexors (P < 0.02) and ankle extensors (P < 0.03), respectively. At the knee, strength of extensors and flexors was reduced by 7% (NS) and 14% (P < 0.05), respectively. At the elbow and wrist, muscle strength was preserved. The NRSS was related to the strength at the ankle (r = -0.45, P < 0.01) and knee (r = -0.42, P < 0.02). Following multiple regression analysis, the NRSS but not the degree of nephropathy or retinopathy was related to strength at the ankle and knee. In conclusion, type 2 diabetic patients may have muscle weakness at the ankle and knee related to presence and severity of peripheral neuropathy.     

Insulin action in muscle and adipose tissue in type 2 diabetes: The significance of blood flow

Under normal metabolic conditions insulin stimulates microvascular perfusion(capillary recruitment) of skeletal muscle and subcutaneous adipose tissue and thus increases blood flow mainly after meal ingestion or physical exercise.This helps the delivery of insulinitself but also that of substrates and of other signalling molecules to multiple tissues beds and facilitates glucose disposal and lipid kinetics.This effect is impaired in insulin resistance and type 2 diabetes early in the development of metabolic dysregulation and reflects early-onset endothelial dysfunction.Failure of insulin to increase muscle and adipose tissue blood flow results in decreased glucose handling.In fat depots,a blunted postprandial blood flow response will result in an insufficient suppression of lipolysis and an increased spill over of fatty acids in the circulation,leading to a more pronounced insulin resistant state in skeletal muscle.This defect in blood flow response is apparent even in the prediabetic state,implying that it is a facet of insulin resistance and exists long before overt hyperglycaemia develops.The following review intends to summarize the contribution of blood flow impairment to the development of the atherogenic dysglycemia and dyslipidaemia.     

Heterogeneity of nephropathies in type 2 diabetes

DIVERSE KIDNEY DISORDERS: Patients with type 2 diabetes mellitus who develop nephropathy can have various types of disorders capable of progressively destroying the kidneys. It is now clear that the same type of diffuse or nodular glomerulosclerosis develops irrespective of the type of diabetes, i.e. the pathophysiology of hyperglycemia. HETEROGENEITY: There is however a certain degree of heterogeneity in terms of clinical presentation, clinical course and response to treatment. Heterogeneity is due to age, the number of different accumulated risk factors and disease states, genetic factors that are in the process of being identified, and finally, lesions to the urologic apparatus, the arteries, and the renal parenchyma itself that are not directly caused by diabetes. PRACTICAL IMPACT: Mixed lesions, due to both diabetic and non-diabetic causes, may therefore exist in the same kidney. These different possibilities should be systematically considered in order to adopt an individualized investigative and therapeutic attitude for each new patient.     

Recombinant human leptin treatment does not improve insulin action in obese subjects with type 2 diabetes

OBJECTIVE

Leptin therapy improves insulin sensitivity in people with leptin deficiency, but it is not known whether it improves insulin action in people who are not leptin deficient. The purpose of the current study was to determine whether leptin treatment has weight loss–independent effects on insulin action in obese subjects with type 2 diabetes.

RESEARCH DESIGN AND METHODS

We conducted a randomized, placebo-controlled trial in obese subjects (BMI: 35.4 ± 0.6 kg/m²; mean ± SE) with newly diagnosed type 2 diabetes. Subjects were randomized to treatment with placebo (saline), low-dose (30 mg/day), or high-dose (80 mg/day) recombinant methionyl human (r-Met hu) leptin for 14 days. Multiorgan insulin sensitivity before and after treatment was evaluated by using the hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotopically labeled tracer infusions to measure glucose, glycerol, and fatty acid kinetics.

RESULTS

Low-dose and high-dose leptin treatment resulted in a threefold (P < 0.01) and 150-fold (P < 0.001) increase in basal plasma leptin concentrations, respectively. However, neither low-dose nor high-dose therapy had an effect on insulin-mediated suppression of glucose, glycerol, or palmitate rates of appearance into plasma compared with placebo. In addition, leptin treatment did not increase insulin-mediated stimulation of glucose disposal compared with placebo (14.3 ± 3.1, 18.4 ± 3.6, 16.7 ± 2.4 vs. 17.5 ± 2.5, 20.7 ± 3.0, 19.1 ± 3.3 μmol/kg body wt/min before vs. after treatment in the placebo, low-dose, and high-dose leptin groups, respectively).

CONCLUSIONS

r-Met hu leptin does not have weight loss–independent, clinically important effects on insulin sensitivity in obese people with type 2 diabetes.Data from studies conducted in animal models indicate that leptin has beneficial effects on insulin action on glucose metabolism (1–3). Leptin also has profound metabolic effects in people. Leptin deficiency is associated with increased body weight and insulin resistance (4), and leptin replacement therapy improves insulin sensitivity in people with congenital leptin deficiency and leptin deficiency as a result of lipodystrophy or HIV-induced lipoatrophy (5–8). In contrast, obesity is commonly associated with insulin resistance despite high plasma leptin concentrations (9–11). Moreover, obesity is associated with resistance to many of the metabolic effects of leptin (12), which has led to the notion that resistance to leptin is involved in the pathogenesis of obesity-related insulin resistance. We hypothesized that increasing plasma leptin concentrations by exogenous leptin administration can improve insulin sensitivity in obese, insulin-resistant subjects. Accordingly, we conducted a randomized, placebo-controlled trial (NCT01207934) to evaluate the effect of low-dose and high-dose leptin treatment on insulin action on glucose production, glucose uptake, and lipolysis (by using a two-stage euglycemic-hyperinsulinemic clamp in conjunction with stable isotopically labeled tracer infusions) in obese subjects with newly diagnosed type 2 diabetes.     

Epidemiology of fractures in type 2 diabetes

Type 2 diabetes affects an increasing proportion of older adults, the population that is also at elevated risk of fracture. Type 2 diabetes itself increases the risk of fracture, particularly in African–American and Latino populations. In Western countries, overweight and obesity, associated with reduced fracture risk, are highly prevalent in diabetic patients. Studies in East Asian countries that have a lower prevalence of obesity with diabetes may help to disentangle the effects of diabetes and obesity on the skeleton. Type 2 diabetes is also associated with higher bone density, and as a result standard tools for fracture prediction tend to underestimate fracture risk in this population, an important challenge for risk assessment in the clinical setting. Contributing factors to the increased fracture risk in type 2 diabetes include more frequent falls and deficits in diabetic bone, not captured by dual X-ray absorptiometry (DXA), that are as yet not clearly understood. Recent epidemiological studies indicate that poor glycemic control contributes to increased fracture risk although intensive lowering of A1C is not effective in preventing fracture.This article is part of a Special Issue entitled “Bone and diabetes”.     

腹腔镜可调控性胃束带术治疗肥胖伴2型糖尿病的机制研究

目的 探讨腹腔镜可调控性胃束带术（LAGB）治疗肥胖症伴2型糖尿病（T2DM）的相关机制.方法 采用LAGB治疗20例肥胖症伴T2DM患者.术后第1、3、6、9、12个月监测术后体质量并计算BMI;采用ELISA检测血清瘦素、胰高血糖素样肽-1（GLP-1）及生长激素释放多肽（ghrein）的水平;采用电化学发光法检测空腹血清胰岛素（FINS）、C肽、糖化血红蛋白（HbA1c）的水平;采用氧化酶法检测空腹血糖（FBG）水平;对血清瘦素、GLP-1及ghrein水平与糖尿病相关指标进行相关性检验.结果 本组20例患者LAGB术后12个月,体质量由术前的（108±18）kg降至（71±16）kg （P＜0.05）,BMI由术前的38±5降至29±6（P＜0.05）;胰岛素抵抗指数由术前的12.8±7.4降至3.4±2.0（P＜0.01）;血清ghrelin水平由术前的（7.8±1.9）μg/L升至（11.6±2.6）μg/L（P＜0.01）,血清瘦素水平由术前（24.9±13.7）μg/L降至（12.9±5.1）μg/L（P＜0.01）,GLP-1水平由术前的（0.58±0.12）μg/L升至（0.80±0.06）μg/L（P＜0.01）;血清瘦素水平与糖尿病相关指标（FBG、FINS、C肽及HbA1c）呈正相关,而血清Ghrelin和GLP-1水平则与上述糖尿病相关指标呈负相关（均P＜0.01）.结论 LAGB能有效治疗肥胖伴T2DM,其可能的机制是通过升高血清GLP-1和ghrelin水平,降低血清瘦素水平,减轻胰岛素抵抗,从而达到降低血糖的目的 .     

Magnesium and type 2 diabetes

Type 2 diabetes is frequently associated with both extracellular and intracellular magnesium(Mg) deficits. A chronic latent Mg deficit or an overt clinical hypomagnesemia is common in patients with type 2 diabetes, especially in those with poorly controlled glycemic profiles. Insulinand glucose are important regulators of Mg metabolism. Intracellular Mg plays a key role in regulating insulin action, insulin-mediated-glucose-uptake and vascular tone. Reduced intracellular Mg concentrations result in a defective tyrosine-kinase activity, postreceptorial impairment in insulin action and worsening of insulin resistance in diabetic patients. A low Mg intake and an increased Mg urinary loss appear the most important mechanisms that may favor Mg depletion in patients with type 2 diabetes. Low dietary Mg intake has been related to the development of type 2 diabetes and metabolic syndrome. Benefits of Mg supplementation on metabolic profiles in diabetic patients have been found in most, but not all clinical studies and larger prospective studies are needed to support the potential role of dietary Mg supplementation as a possible public health strategy in diabetes risk. The aim of this review is to revise current evidence on the mechanisms of Mg deficiency in diabetes and on the possible role of Mg supplementation in the prevention and management of the disease.