Comparison of Glucose Lowering Effect of Metformin and Acarbose in Type 2 Diabetes Mellitus: A Meta-Analysis

BackgroundMetformin is the first-line oral hypoglycemic agent for type 2 diabetes mellitus recommended by international guidelines. However, little information exists comparing it with acarbose which is also commonly used in China. This study expanded knowledge by combining direct and indirect evidence to ascertain the glucose lowering effects of both drugs.MethodsPubMed (1980- December 2013) and China National Knowledge Infrastructure databases (1994-January 2014) were systematically searched for eligible randomized controlled trials from Chinese and English literatures. Meta-analysis was conducted to estimate the glucose lowering effects of metformin vs. acarbose, or either of them vs. common comparators (placebo or sulphonylureas), using random- and fixed-effect models. Bucher method with indirect treatment comparison calculator was applied to convert the summary estimates from the meta-analyses into weighted-mean-difference (WMD) and 95% confidence intervals (CIs) to represent the comparative efficacy between metformin and acarbose.ResultsA total of 75 studies were included in the analysis. In direct comparison (8 trials), metformin reduced glycosylated hemoglobin (HbA_1c) by 0.06% more than acarbose, with no significant difference (WMD,-0.06%; 95% CI, -0.32% to 0.20%). In indirect comparisons (67 trials), by using placebo and sulphonylureas as common comparators, metformin achieved significant HbA_1c reduction than acarbose, by -0.38% (WMD,-0.38%, 95% CI, -0.736% to -0.024%) and -0.34% (WMD, -0.34%, 95% CI, -0.651% to -0.029%) respectively.ConclusionThe glucose lowering effects of metformin monotherapy and acarbose monotherapy are the same by direct comparison, while metformin is a little better by indirect comparison. This implies that the effect of metformin is at least as good as acarbose''s.     

The Dawn Phenomenon Revisited: Implications for Diabetes Therapy

ObjectiveTo summarize current data on the magnitude, prevalence, variability, pathogenesis, and management of the dawn phenomenon in patients with diabetes mellitus.MethodsOn the basis of the pertinent available literature and clinical experience, we propose a quantitative definition of the dawn phenomenon, discuss potential pathogenic mechanisms, and suggest management options.ResultsThe “dawn phenomenon” is a term used to describe hyperglycemia or an increase in the amount of insulin needed to maintain normoglycemia, occurring in the absence of antecedent hypoglycemia or waning insulin levels, during the early morning hours. To be clinically relevant, the magnitude of the dawn increase in blood glucose level should be more than 10 mg/dL or the increase in insulin requirement should be at least 20% from the overnight nadir. Controversy exists regarding the frequency, reproducibility, and pathogenesis of the dawn phenomenon. Approximately 54% of patients with type 1 diabetes and 55% of patients with type 2 diabetes experience the dawn phenomenon when the foregoing quantitative definition is used. The most likely pathogenic mechanism underlying the dawn phenomenon is growth hormone-mediated impairment of insulin sensitivity at the liver and muscles. The exact biochemical pathways involved are unknown. Therapeutic decisions aimed at correcting fasting hyperglycemia should take into account the variability and magnitude of the dawn phenomenon within individual patients. Successful insulinization appears to minimize the effects of the dawn phenomenon. Currently, no subcutaneous depot preparation of insulin exists that is capable of mimicking the basal insulinsecretion of the healthy pancreas.ConclusionIncreases in the bedtime doses of hypoglycemic agents with nighttime peaks in action may correct early morning hyperglycemia but be associated with undesirable nocturnal hypoglycemia. Targeted continuous subcutaneous insulin infusion programming can facilitate the prevention of early morning hyperglycemia in selected patients. (Endocr Pract. 2005;11:55-64)     

Inhibition of Renal Glucose Reabsorption: A Novel Strategy for Achieving Glucose Control in Type 2 Diabetes Mellitus

ObjectiveTo review the renal handling of glucose and the role of inhibition of a sodium-glucose transporter (SGLT2) in the treatment of type 2 diabetes mellitus (T2DM).MethodsWe review the published data about (1) the filtration and reabsorption of glucose by the kidneys in normal subjects and patients with diabetes; (2) the deleterious effects of long-term elevation of plasma glucose levels on muscle and hepatic insulin sensitivity and beta cell function (that is, glucotoxicity); (3) the effect of inhibiting the SGLT2 transporter on the induction of glycosuria, glycemic control, insulin resistance, and beta cell dysfunction in animals and humans with diabetes; and (4) the safety of SGLT2 inhibition as a therapeutic modality to treat human T2DM.ResultsStudies in animal models of diabetes document the efficacy of the SGLT2 inhibitors in inducing glycosuria, decreasing both fasting and postprandial glucose levels, augmenting beta cell function, and enhancing hepatic and muscle insulin sensitivity. In human T2DM, short-term studies with dapagliflozin (12 weeks) and sergliflozin (2 weeks) have confirmed the efficacy of these agents in improving glycemic control. Excessive urinary electrolyte or water loss, plasma electrolyte disturbances, and hypoglycemia were not observed.ConclusionSGLT2 inhibitors represent a promising approach to the treatment of T2DM. They have the potential to be used as monotherapy, as well as in combination with all approved antidiabetic agents. Because their mechanism of action is independent of the severity of beta cell dysfunction or insulin resistance, efficacy should not decline with progressive beta cell failure or in the presence of severe insulin resistance. (Endocr Pract. 2008;14:782-790)     

Fixed-Dose Combination Therapy in Type 2 Diabetes Mellitus

ObjectiveThe management of type 2 diabetes mellitus (T2DM) often requires combinations of antihyperglycemic medications with complementary mechanisms of action. Inadequate adherence to combination therapy, possibly related to pill burden (greater number of pills and higher administration frequency) and poor tolerability, may lead to suboptimal clinical outcomes. One potential means of addressing these problems is the use of fixed-dose combinations (FDCs) that simplify the treatment regimen by reducing pill burden compared with the same combination delivered as separate pills. The present study evaluates the efficacy and tolerability of FDCs in the treatment of T2DM patients and provides an overview of dosing, costs, and adherence.MethodsA review of FDCs, with particular attention to those that contain metformin extended-release (XR) and allow once-daily dosing.ResultsMany FDCs contain metformin as one of the component drugs. However, the standard immediate-release (IR) formulation of metformin requires twice-daily dosing and may have tolerability problems related to adverse gastrointestinal (GI) effects. The XR formulationsof metformin can be administered once daily and have been shown to reduce the occurrence of GI effects frequently observed with metformin IR; consequently, they may have significant advantages for inclusion in FDCs. The long-term cost-effectiveness of FDCs remains to be fully determined.ConclusionFor patients taking metformin, FDCs containing metformin XR offer equivalent efficacy with reduced dose frequency and, potentially, fewer GI events compared with standard IR formulation, as well as a reduced number of pills compared with separate-pill regimens. By reducing pill burden and improving tolerability, FDCs may improve adherence. (Endocr Pract. 2014;20: 1322-1332)     

Implications of Magnesium Deficiency in Type 2 Diabetes: A Review

Magnesium is the fourth most abundant cation in the body and plays an important physiological role in many of its functions. It plays a fundamental role as a cofactor in various enzymatic reactions involving energy metabolism. Magnesium is a cofactor of various enzymes in carbohydrate oxidation and plays an important role in glucose transporting mechanism of the cell membrane. It is also involved in insulin secretion, binding, and activity. Magnesium deficiency and hypomagnesemia can result from a wide variety of causes, including deficient magnesium intake, gastrointestinal, and renal losses. Chronic magnesium deficiency has been associated with the development of insulin resistance. The present review discusses the implications of magnesium deficiency in type 2 diabetes.     

Insulin Therapy and Hypoglycemia in Type 2 Diabetes Mellitus

Background: Iatrogenic hypoglycemia, the limiting factor in the glycemic management of diabetes mellitus (DM), is the result of therapeutic insulin excess and compromised physiological and behavioral defenses against falling plasma glucose concentrations.Objective: The goal of this article was to review the available evidence on insulin therapy and hypoglycemia, with a focus on type 2 DM.Methods: This review was based on the author's clinical experience, his >3 decades of translational research in the area of hypoglycemia, and his knowledge of the relevant preclinical and clinical literature.Results: Glycemic defenses become compromised rapidly in type 1 DM but slowly in type 2 DM. As a result, the frequency of hypoglycemia increases progressively as patients approach the insulin-deficient end of the spectrum of type 2 DM. Indeed, it appears that most episodes of hypoglycemia, including those of severe hypoglycemia, occur in individuals with type 2 DM. The conventional risk factors for hypoglycemia are based on relative or absolute insulin excess. It is clear that the pathogenesis of hypoglycemia-associated autonomic failure, and thus an increased risk for iatrogenic hypoglycemia, stems fundamentally from insulin deficiency. Relevant additional risk factors include the degree of insulin deficiency, a history of severe hypoglycemia, hypoglycemia unawareness, or both, as well as recent antecedent hypoglycemia, prior exercise and sleep, and aggressive glycemic therapy per se in advanced type 2 DM, just as in type 1 DM. The prevention of hypoglycemia involves the practice of hypoglycemia risk reductionȔdiscussion of the issue, application of the principles of aggressive therapy, and consideration of both the conventional risk factors and those relevant to compromised glycemic defensesȔin advanced type 2 DM, just as in type 1 DM. With this approach, it is possible to improve glycemic control and reduce the frequency of hypoglycemia in many people with DM.Conclusions: Pending the prevention and cure of DM, people with this disease need safe and effective therapies. Ultimately, that will require glucose-regulated insulin replacement or secretion. In the meantime, insight into the mechanisms of hypoglycemia-associated autonomic failure may lead to interventions that will further improve the lives of people affected by DM by reducing the frequency of hypoglycemia without compromising glycemic control.(Insulin. 2007;2:127-133)     

雌性小鼠不适于构建HFD-STZ联合诱导的2型糖尿病模型

目的 探讨雌性小鼠在高脂饲料(HFD)-链脲佐菌素(STZ)联合诱导2型糖尿病模型中的可行性.方法 分别以高脂饲料、高脂饲料-果糖饮水(HFDF)和常规饲料(对照)喂养3周龄的封闭群ICR和近交系C57BL/6J (B6)小鼠6周后,HFD和HFDF组腹腔注射STZ,对照组注射相应体积柠檬酸钠溶液,然后分别以相应饲料继续喂养6周.每周测定小鼠体重,于注射前1周和注射后1～4周测定非空腹血糖浓度.结果 实验结束时各组小鼠体重较初始体重均显著增加.ICR小鼠HFD和HFDF组体重与对照组S无差异,HFD与HFDF组间也无显著变化.虽然B6小鼠HFD与HFDF组体重组间差异不显著,但两组体重均显著低于对照组.注射STZ后1～4周,两品系小鼠HFD与HFDF组血糖水平没有显著升高,组间也没有显著差异,且均没有达到2型糖尿病小鼠成模非空腹血糖标准(11 mmol/L).结论 果糖饮水不能促进高脂饲料诱导的育肥作用,而雌性小鼠也不是HFD-STZ联合诱导2型糖尿病模型的理性选择.     

Impaired Increase of Plasma Abscisic Acid in Response to Oral Glucose Load in Type 2 Diabetes and in Gestational Diabetes

The plant hormone abscisic acid (ABA) is present and active in humans, regulating glucose homeostasis. In normal glucose tolerant (NGT) human subjects, plasma ABA (ABAp) increases 5-fold after an oral glucose load. The aim of this study was to assess the effect of an oral glucose load on ABAp in type 2 diabetes (T2D) subjects. We chose two sub-groups of patients who underwent an oral glucose load for diagnostic purposes: i) 9 treatment-naive T2D subjects, and ii) 9 pregnant women with gestational diabetes (GDM), who underwent the glucose load before and 8–12 weeks after childbirth. Each group was compared with matched NGT controls. The increase of ABAp in response to glucose was found to be abrogated in T2D patients compared to NGT controls. A similar result was observed in the women with GDM compared to pregnant NGT controls; 8–12 weeks after childbirth, however, fasting ABAp and ABAp response to glucose were restored to normal in the GDM subjects, along with glucose tolerance. We also retrospectively compared fasting ABAp before and after bilio-pancreatic diversion (BPD) in obese, but not diabetic subjects, and in obese T2D patients, in which BPD resulted in the resolution of diabetes. Compared to pre-BPD values, basal ABAp significantly increased 1 month after BPD in T2D as well as in NGT subjects, in parallel with a reduction of fasting plasma glucose. These results indicate an impaired hyperglycemia-induced ABAp increase in T2D and in GDM and suggest a beneficial effect of elevated ABAp on glycemic control.     

Periodontal Therapy and Systemic Inflammation in Type 2 Diabetes Mellitus: A Meta-Analysis

Aim

The aim of this systematic review was to assess the effect of periodontal therapy (PT) on serum levels of inflammatory markers in people with type 2 diabetes mellitus (T2DM).

Methods of Study Selection

A literature search was carried out using MEDLINE via Pubmed, EMBASE, LILACS and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Randomized-controlled trials (RCTs) and controlled clinical trials (CCTs) evaluating the effect of PT on systemic inflammatory markers were deemed eligible. Case series (CS), reports and pilot trials were excluded. Study quality was assessed using the Cochrane Collaboration’s risk assessment tool. Meta-analysis was carried out using random effect methods.

Results

The search strategy identified 3,164 potential studies of which 61 were assessed for eligibility and 9 (6 RCTs and 3 CCTs) were included in this systematic review. Three RCTs were classified by the authors as being at low risk of bias and three were “unclear” and classified as uncertain risk of bias. All CCTs were considered to be at a high risk of bias. The meta-analysis showed a statistically significant mean difference (MD) for TNF- α (-1.33 pg/ml, 95% CI: -2.10; -0.56, p<0.001) and CRP (-1.28 mg/l, 95% CI: -2.07; - 0.48, p<0.001) favoring periodontal intervention versus control.

Conclusion

The results of this meta-analysis support the hypothesis that PT reduces serum levels of TNF- α and CRP in T2DM individuals. The decrease of inflammatory burden has important implications for metabolic control and can, in part, explain the mechanisms linking periodontitis and increased risk for complications in people with T2DM.     

Quality of Life and Insulin Therapy in Type 2 Diabetes Mellitus

Background: A frequently cited barrier to insulin use in type 2 diabetes mellitus (DM) is concern about the adverse effects on quality of life. Results of studies in this area have been mixed, with insulin use showing decreased, enhanced, or no impact on quality of life.Objective: The purpose of this paper is to discuss the state of the science regarding the effects of insulin on quality of life and to present strategies providers can implement in their clinical practices to decrease barriers to insulin use among patients with type 2 DM.Methods: An English-language MEDLINE search of the current literature using the terms insulin and quality of life was conducted for this article.Results: Although patient-identified concerns regarding insulin use represent some aspects of quality of life, study results have been mixed. However, 2 large studies examining the use of insulin glargine and its effects on quality of life found that glargine was associated with significantly greater improvements in quality of life when added to oral antidiabetic agents (OADs) than was the use of OADs alone. Another study examined the effects of intensive multi- therapy (monthly visits, self-management diabetes education, and medication adjustments) on quality of life among patients with type 2 DM and found that quality-of-life scores improved among patients who initiated insulin therapy during the trial. The effects of insulin delivery systems on quality of life have also been assessed. In these studies, patients preferred insulin pens over vials and syringes and inhaled over injected insulin. Health care providers can facilitate acceptance of insulin by employing strategies to help patients overcome psychological barriers to insulin therapy.Conclusions: Although patient concerns about the effects of insulin use are legitimate, insulin therapy is often needed to achieve treatment targets. Providers can reduce the impact on quality of life by addressing barriers, helping patients improve metabolic control, and providing ongoing information and support.     

Modulation of Glucose Transporter Protein by Dietary Flavonoids in Type 2 Diabetes Mellitus

Diabetes mellitus (DM) is a metabolic diseases characterized by hyperglycemia due to insufficient or inefficient insulin secretory response. This chronic disease is a global problem and there is a need for greater emphasis on therapeutic strategies in the health system. Phytochemicals such as flavonoids have recently attracted attention as source materials for the development of new antidiabetic drugs or alternative therapy for the management of diabetes and its related complications. The antidiabetic potential of flavonoids are mainly through their modulatory effects on glucose transporter by enhancing GLUT-2 expression in pancreatic β cells and increasing expression and promoting translocation of GLUT-4 via PI3K/AKT, CAP/Cb1/TC10 and AMPK pathways. This review highlights the recent findings on beneficial effects of flavonoids in the management of diabetes with particular emphasis on the investigations that explore the role of these compounds in modulating glucose transporter proteins at cellular and molecular level.     

Cell Membrane Integrity in Myotonic Dystrophy Type 1: Implications for Therapy

Myotonic Dystrophy type 1 (DM1) is a multisystemic disease caused by toxic RNA from a DMPK gene carrying an expanded (CTG•CAG)n repeat. Promising strategies for treatment of DM1 patients are currently being tested. These include antisense oligonucleotides and drugs for elimination of expanded RNA or prevention of aberrant binding to RNP proteins. A significant hurdle for preclinical development along these lines is efficient systemic delivery of compounds across endothelial and target cell membranes. It has been reported that DM1 patients show elevated levels of markers of muscle damage or loss of sarcolemmal integrity in their serum and that splicing of dystrophin, an essential protein for muscle membrane structure, is abnormal. Therefore, we studied cell membrane integrity in DM1 mouse models commonly used for preclinical testing. We found that membranes in skeletal muscle, heart and brain were impermeable to Evans Blue Dye. Creatine kinase levels in serum were similar to those in wild type mice and expression of dystrophin protein was unaffected. Also in patient muscle biopsies cell surface expression of dystrophin was normal and calcium-positive fibers, indicating elevated intracellular calcium levels, were only rarely seen. Combined, our findings indicate that cells in DM1 tissues do not display compromised membrane integrity. Hence, the cell membrane is a barrier that must be overcome in future work towards effective drug delivery in DM1 therapy.     

Aerobic and Combined Exercise Sessions Reduce Glucose Variability in Type 2 Diabetes: Crossover Randomized Trial

Purpose

To evaluate the effects of aerobic (AER) or aerobic plus resistance exercise (COMB) sessions on glucose levels and glucose variability in patients with type 2 diabetes. Additionally, we assessed conventional and non-conventional methods to analyze glucose variability derived from multiple measurements performed with continuous glucose monitoring system (CGMS).

Methods

Fourteen patients with type 2 diabetes (56±2 years) wore a CGMS during 3 days. Participants randomly performed AER and COMB sessions, both in the morning (24 h after CGMS placement), and at least 7 days apart. Glucose variability was evaluated by glucose standard deviation, glucose variance, mean amplitude of glycemic excursions (MAGE), and glucose coefficient of variation (conventional methods) as well as by spectral and symbolic analysis (non-conventional methods).

Results

Baseline fasting glycemia was 139±05 mg/dL and HbA1c 7.9±0.7%. Glucose levels decreased immediately after AER and COMB protocols by ∼16%, which was sustained for approximately 3 hours. Comparing the two exercise modalities, responses over a 24-h period after the sessions were similar for glucose levels, glucose variance and glucose coefficient of variation. In the symbolic analysis, increases in 0 V pattern (COMB, 67.0±7.1 vs. 76.0±6.3, P = 0.003) and decreases in 1 V pattern (COMB, 29.1±5.3 vs. 21.5±5.1, P = 0.004) were observed only after the COMB session.

Conclusions

Both AER and COMB exercise modalities reduce glucose levels similarly for a short period of time. The use of non-conventional analysis indicates reduction of glucose variability after a single session of combined exercises.

Trial Registration

Aerobic training, aerobic-resistance training and glucose profile (CGMS) in type 2 diabetes (CGMS exercise). ClinicalTrials.gov ID: {"type":"clinical-trial","attrs":{"text":"NCT00887094","term_id":"NCT00887094"}}NCT00887094.     

Kinetic Modeling of Human Hepatic Glucose Metabolism in Type 2 Diabetes Mellitus Predicts Higher Risk of Hypoglycemic Events in Rigorous Insulin Therapy

A major problem in the insulin therapy of patients with diabetes type 2 (T2DM) is the increased occurrence of hypoglycemic events which, if left untreated, may cause confusion or fainting and in severe cases seizures, coma, and even death. To elucidate the potential contribution of the liver to hypoglycemia in T2DM we applied a detailed kinetic model of human hepatic glucose metabolism to simulate changes in glycolysis, gluconeogenesis, and glycogen metabolism induced by deviations of the hormones insulin, glucagon, and epinephrine from their normal plasma profiles. Our simulations reveal in line with experimental and clinical data from a multitude of studies in T2DM, (i) significant changes in the relative contribution of glycolysis, gluconeogenesis, and glycogen metabolism to hepatic glucose production and hepatic glucose utilization; (ii) decreased postprandial glycogen storage as well as increased glycogen depletion in overnight fasting and short term fasting; and (iii) a shift of the set point defining the switch between hepatic glucose production and hepatic glucose utilization to elevated plasma glucose levels, respectively, in T2DM relative to normal, healthy subjects. Intriguingly, our model simulations predict a restricted gluconeogenic response of the liver under impaired hormonal signals observed in T2DM, resulting in an increased risk of hypoglycemia. The inability of hepatic glucose metabolism to effectively counterbalance a decline of the blood glucose level becomes even more pronounced in case of tightly controlled insulin treatment. Given this Janus face mode of action of insulin, our model simulations underline the great potential that normalization of the plasma glucagon profile may have for the treatment of T2DM.     

Postprandial Dynamics of Plasma Glucose,Insulin, and Glucagon in Patients with Type 2 Diabetes Treated with Saxagliptin Plus Dapagliflozin Add-On to Metformin Therapy

ObjectiveTo analyze changes in plasma glucose, insulin, and glucagon in relation to glycemic response during treatment with dual add-on of saxagliptin (SAXA) plus dapagliflozin (DAPA) to metformin XR (MET) compared with SAXA add-on or DAPA add-on alone to MET in patients with type 2 diabetes mellitus (T2DM) poorly controlled with MET.MethodsDouble-blind trial in adults with glycated hemoglobin (HbAlc) ≥ 8.0 to ≤ 12.0% randomized to SAXA 5 mg/day plus DAPA 10 mg/day (n = 179), or SAXA 5 mg/day and placebo (n = 176), or DAPA 10 mg/day and placebo (n = 179) added to background MET ≥ 1,500 mg/ day. The mean change from baseline in the area under the curve from 0 to 180 minutes (AUC_{0-180 min}) was calculated for glucose, insulin, and glucagon obtained during a liquid meal tolerance test (MTT).ResultsGlucose AUC_{0-180 min} an was reduced more from baseline with SAXA + DAPA + MET (-12,940 mg/dL) compared with SAXA + MET (-6,309 mg/dL) and DAPA + MET (-11,247 mg/dL). Insulin AUC_{0-180 min} significantly decreased with SAXA + DAPA + MET (-1,120 μU/mL) and DAPA + MET (-1,019 μU/mL) and increased with SAXA + MET (661 μU/mL). Glucagon AUC_{0-180 min} only increased with DAPA + MET (2,346 pg/mL). The changes in glucose (P < .0001) and insulin (P = .0003) AUC_{0-180 min} correlated with change in HbA1c, whereas the change in glucagon AUC_{0-180 min} min did not (P = .27).ConclusionsWhen added to background MET, the combination of SAXA + DAPA provided additional reductions in glucose AUC_{0-180 min} and HbA1c without the increase in insulin seen with SAXA and without the increase in glucagon seen with DAPA. Changes in insulin and glucose but not glucagon AUC_{0-180 min} correlated with change in HbA1c. (Endocr Pract. 2014;20:1187-1197)     

干细胞在 1 型糖尿病治疗中的应用研究进展

1型糖尿病（T1D）是一种慢性、多因素自身免疫性疾病,在发病过程中,会不断破坏胰岛β细胞,最终导致胰岛素分泌不足, 严重威胁人类健康。目前,根治T1D的主要方法是胰岛移植,即将移植的胰岛替代体内已被疾病破坏的胰岛细胞,以恢复正常血糖。但 是,胰岛移植供体的缺乏和移植免疫排斥反应,给胰岛移植的临床应用带来巨大挑战。近年来,干细胞治疗为T1D提供了一种新疗法, 成为T1D治疗领域新的研究热点,为该病的治疗提供了新思路。综述不同来源干细胞——胚胎干细胞、诱导多能干细胞和成体干细胞用 于治疗T1D的研究进展。     

Recombinant Adiponectin Does Not Lower Plasma Glucose in Animal Models of Type 2 Diabetes

Aims/Hypothesis

Several studies have shown that adiponectin can lower blood glucose in diabetic mice. The aim of this study was to establish an effective adiponectin production process and to evaluate the anti-diabetic potential of the different adiponectin forms in diabetic mice and sand rats.

Methods

Human high molecular weight, mouse low molecular weight and mouse plus human globular adiponectin forms were expressed and purified from mammalian cells or yeast. The purified protein was administered at 10–30 mg/kg i.p. b.i.d. to diabetic db/db mice for 2 weeks. Furthermore, high molecular weight human and globular mouse adiponectin batches were administered at 5–15 mg/kg i.p. b.i.d. to diabetic sand rats for 12 days.

Results

Surprisingly, none of our batches had any effect on blood glucose, HbA1c, plasma lipids or body weight in diabetic db/db mice or sand rats. In vitro biological, biochemical and biophysical data suggest that the protein was correctly folded and biologically active.

Conclusions/Interpretation

Recombinant adiponectin is ineffective at lowering blood glucose in diabetic db/db mice or sand rats.