Combined metformin and insulin therapy for patients with type 2 diabetes mellitus

OBJECTIVE: This study was undertaken to assess the effects of combined treatment with insulin and metformin in patients with type 2 diabetes mellitus in whom dietary measures, weight control, and oral antihyperglycemic therapy had failed. BACKGROUND: Insulin resistance in peripheral tissues, increased hepatic gluconeogenesis, and impaired insulin secretion are the underlying factors in the development of type 2 diabetes. Metformin is a biguanide antihyperglycemic agent that increases peripheral insulin sensitivity, reduces hepatic gluconeogenesis, and decreases intestinal glucose absorption. METHODS: Thirty-one patients (24 women, 7 men; mean age, 61.8 years; mean body mass index [BMI], 28.0 kg/m2) were enrolled in this randomized, double-blind, 2-way, crossover, placebo-controlled study. Patients with type 2 diabetes who were treated previously with insulin or oral hypoglycemic agents and who had a glycosylated hemoglobin (HbA1c) level >9% or a fasting blood glucose level >8 mmol/L were included. Patients who were being treated with oral agents were switched to insulin therapy and required to maintain stable blood glucose control for 2 months prior to randomization. Patients received insulin plus either metformin 1,700 mg/d or placebo for 5 months, followed by a 2-month washout period, and were then crossed over to the other treatment arm for 5 months of additional treatment (total treatment period: 12 months). RESULTS: Thirty patients completed the study; 1 patient withdrew early because of hypoglycemia. Compared with placebo, metformin produced significant reductions from overall baseline in mean daily insulin dose requirement (-8.69 units (17.2%], P < 0.001), HbA1c level (-0.74 [9.9%], P = 0.005), serum fructosamine level (-44.40 micromol/L, P = 0.026), 24-hour blood glucose profile (P = 0.008), and total cholesterol level (-0.42 mmol/L, P = 0.005). No treatment effects were observed on body weight, blood pressure, serum high-density lipoprotein cholesterol levels, or serum triglyceride levels. There was no correlation between BMI and reduction in HbA1C. No major side effects were reported. CONCLUSIONS: Combination therapy with metformin and insulin improves glycemic control and reduces insulin requirements. with no major side effects, in patients with type 2 diabetes and may improve the risk profile in this patient population.     

Reduced hypoglycemia risk with insulin glargine: a meta-analysis comparing insulin glargine with human NPH insulin in type 2 diabetes

OBJECTIVE: Insulin glargine (LANTUS) is a once-daily basal insulin analog with a smooth 24-h time-action profile that provides effective glycemic control with reduced hypoglycemia risk (particularly nocturnal) compared with NPH insulin in patients with type 2 diabetes. A recent "treat-to-target" study has shown that more patients on insulin glargine reached HbA(1c) levels < or =7.0% without confirmed nocturnal hypoglycemia compared with NPH insulin. We further assessed the risk for hypoglycemia in a meta-analysis of controlled trials of a similar design for insulin glargine versus once- or twice-daily NPH insulin in adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: All studies were 24-28 weeks long, except one 52-week study, for which interim 20-week data were used. RESULTS: Patient demographics were similar between the insulin glargine (n = 1,142) and NPH insulin (n = 1,162) groups. The proportion of patients achieving target HbA(1c) (< or =7.0%) was similar between insulin glargine-and NPH insulin-treated patients (30.8 and 32.1%, respectively). There was a consistent significant reduction of hypoglycemia risk associated with insulin glargine, compared with NPH insulin, in terms of overall symptomatic (11%; P = 0.0006) and nocturnal (26%; P < 0.0001) hypoglycemia. Most notably, the risk of severe hypoglycemia and severe nocturnal hypoglycemia were reduced with insulin glargine by 46% (P = 0.0442) and 59% (P = 0.0231), respectively. CONCLUSIONS: These results confirmed that insulin glargine given once daily reduces the risk of hypoglycemia compared with NPH insulin, which can facilitate more aggressive insulin treatment to a HbA(1c) target of < or =7.0% in patients with type 2 diabetes.     

2型糖尿病患者发生认知功能障碍危险因素的Meta分析

目的系统评价2型糖尿病认知功能障碍危险因素。方法通过检索中英文数据库,筛选符合纳入标准的队列研究文献,应用Rev Man 5.3分析软件对资料进行分析。结果 1 910篇文献中21篇文献符合纳入标准,共纳入40个危险因素。经Meta分析,合并效应量具有统计学意义的RR值(95%CI)分别为女性1.21(1.16,1.25)、受教育程度0.81(0.77,0.85)、低血糖1.34(1.26,1.42)、脑血管疾病史1.46(1.08,1.99)、卒中史2.23(1.51,3.28)、肾病1.45(1.39,1.52)、视网膜病变1.35(1.21,1.51)、神经病变1.14(1.06,1.23)、降糖药物的使用1.10(1.04,1.16)、胰岛素的使用1.43(1.33,1.54)、抑郁1.38(1.32,1.45)。结论女性、低血糖、脑血管疾病史、卒中史、肾病、视网膜病变、神经病变、降糖药物使用、胰岛素使用、抑郁是认知功能障碍的危险因素,受教育程度是认知障碍的保护因素,而年龄、种族、糖尿病足、糖化血红蛋白、高血脂、高血压与认知功能障碍的关系在本研究中显示无统计学意义,有待开展大样本前瞻性队列研究予以验证。     

Long-term efficacy of metformin therapy in nonobese individuals with type 2 diabetes

OBJECTIVE: The U.K. Prospective Diabetes Study (UKPDS) has demonstrated that metformin is as effective as sulfonylureas in obese subjects and is associated with less weight gain, fewer hypoglycemic episodes, and better cardiovascular outcomes. It is hence the pharmacological therapy of choice in this subgroup. However, a gap in our present knowledge is the long-term response to metformin in nonobese individuals. In this study, we compared metformin therapy in normal, overweight, and obese individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: A database of patients treated at a referral center in Sydney, Australia, were analyzed. Patients with type 2 diabetes and complete HbA(1c) (A1C) data and treated with metformin or sulfonylurea monotherapy for at least three visits before receiving dual oral therapy were included (n = 644). Analysis by BMI and the type of oral agent was performed. Individuals were categorized as normal, overweight, or obese (BMI <25, 25-29.9, and >/=30 kg/m(2), respectively). RESULTS: There were no differences between the initial, follow-up, and last A1C between the three metformin-treated groups. The duration of successful glycemic control with metformin monotherapy in the normal and overweight individuals and their incidences of diabetes-related complications for the entire duration of follow-up were not inferior to those of the obese individuals. The nonobese patients performed better regardless of the type of oral hypoglycemic agent used. CONCLUSIONS: We conclude that metformin is at least as efficacious in normal and overweight individuals as it is in those who are obese. Our study provides evidence-based data to support metformin use in nonobese individuals with type 2 diabetes.     

吸烟与2型糖尿病发生风险关系前瞻性研究的meta分析

目的 探讨吸烟与2型糖尿病的关系及风险效应.方法 采用meta分析方法,对国内外21篇关于吸烟与2型糖尿病关系 的前瞻性研究进行定量分析.结果 现吸烟、戒烟合并RR值(95％CI)分别为1.42(1.14,1.77),1.37(1.16,1.61),吸烟(＜20支/d)、吸烟(≥20支/d)合并RR值(95％CI)分别为1.12(0.87,1.43),1.45(1.03,2.04),男、女性吸烟合并RR值(95％CI)分别为1.35(1.15,1.60),0.77(0.63,0.96).结论 不同吸烟状态不仅是2型糖尿病发生的风险因素,且不同性别随着吸烟量的增加,2型糖尿病的发生风险不同.     

Advantages of extended-release metformin in patients with type 2 diabetes mellitus

Metformin is a first-line pharmacological treatment for patients with type 2 diabetes mellitus because of its favorable overall profile, including its glucose-lowering ability, weight-neutral effects, and low risk of hypoglycemia; however, gastrointestinal (GI) intolerance may limit use in some patients. Extended-release metformin improves GI tolerability, allows once-daily dosing, and is currently available in multiple branded and generic formulations; however, it is more expensive than immediate-release metformin. Maximum plasma metformin concentrations are reached more slowly with the extended-release formulation compared with conventional immediate-release metformin, although both provide similar exposure at a given total daily dose. Extended-release metformin is as effective as immediate-release metformin in patients newly started on metformin and those switched from the immediate-release formulation, with similar weight-neutral effects. Tolerability is generally comparable, although patients switched from the immediate-release formulation--even those switched due to GI intolerance--are often better able to tolerate the extended-release formulation. Based on studies of extended-release formulations in other disease states, metformin extended-release formulation has the potential to improve patient adherence with a simpler dosing regimen and increased tolerability. Increased adherence may result in greater glycemic control, and in turn, improve outcomes and lower health care usage and costs. Extended-release metformin provides an appropriate option for patients with type 2 diabetes mellitus who require several medications to achieve glycemic control or manage comorbid conditions, and for those who have GI intolerance with the immediate-release formulation.     

Differential effects of metformin and troglitazone on cardiovascular risk factors in patients with type 2 diabetes

OBJECTIVE: Traditional cardiovascular risk factors (CVRF) only partly explain the excessive risk of cardiovascular disease in patients with type 2 diabetes. There is now an increasing appreciation for many novel CVRF that occur largely as a result of insulin resistance and hyperinsulinemia. Therefore, we investigated whether diabetes medications that vary in their mechanism of action and ability to reduce insulin resistance may differ in their effects on both traditional and novel CVRF. RESEARCH DESIGN AND METHODS: We compared the addition of metformin or troglitazone therapy on CVRF in 22 subjects with type 2 diabetes who remained in poor glycemic control (with HbA1c >8.5%) while taking glyburide 10 mg twice daily. Subjects were initially randomized to either metformin 850 mg once daily or troglitazone 200 mg once daily. Both medications were then titrated upward as needed to achieve fasting plasma glucose <120 mg/dl. Measures of glucose control, insulin resistance, and CVRF (blood pressure, lipids, plasminogen activator inhibitor-1, C-reactive protein, fibrinogen, and small dense LDL) were assessed both before and after therapy. RESULTS: After 4 months of treatment, both metformin and troglitazone led to similar decreases in fasting plasma glucose and HbA1c. The reduction in insulin resistance determined by hyperinsulinemic-euglycemic clamp was nearly twofold greater with troglitazone than metformin. Metformin did not induce significant changes in blood pressure, LDL cholesterol, LDL size, HDL cholesterol, triglycerides, or plasminogen activator inhibitor-1. However, C-reactive protein did decrease by 33% (6 +/- 1 to 4 +/- 1 mg/l; P < 0.01) [corrected]. Troglitazone therapy was associated with increases in LDL size (26.21 +/- 0.22 to 26.56 +/- 0.25 nm; P=0.04) and HDL cholesterol (33 +/- 3 to 36 +/- 3 mg/dl; P=0.05) and decreases in triglycerides (197 +/- 19 to 155 +/- 23 mg/dl; P=0.07) and C-reactive protein by 60% (8 +/- 3 to 3 +/- 1 mg/l, P < 0.01) [corrected]. CONCLUSIONS: For patients with type 2 diabetes in whom maximal sulfonylurea therapy failed, the addition of the insulin sensitizer troglitazone seemed to have greater benefits on several traditional and novel CVRF than metformin therapy. These differences were not related to glycemic improvement but reflected, in part, the greater reduction in insulin resistance obtained with addition of troglitazone. These data suggest that medications that more effectively address this underlying metabolic defect may be more beneficial in reducing cardiovascular risk in type 2 diabetes.     

Effect of metformin in pediatric patients with type 2 diabetes: a randomized controlled trial.

OBJECTIVE: Metformin is the most commonly prescribed oral antidiabetic agent in the U.S. for adults with type 2 diabetes. The incidence of type 2 diabetes in children has increased dramatically over the past 10 years, and yet, metformin has never been formally studied in children with type 2 diabetes. RESEARCH DESIGN AND METHODS: This study evaluated the safety and efficacy of metformin at doses up to 1,000 mg twice daily in 82 subjects aged 10-16 years for up to 16 weeks in a randomized double-blind placebo-controlled trial from September 1998 to November 1999. Subjects with type 2 diabetes were enrolled if they had a fasting plasma glucose (FPG) levels > or =7.0 and < or =13.3 mmol/l (> or =126 and < or =240 mg/dl), HbA(1c) > or =7.0%, stimulated C-peptide > or =0.5 nmol/l (> or =1.5 ng/ml), and a BMI > 50th percentile for age. RESULTS: Metformin significantly improved glycemic control. At the last double-blind visit, the adjusted mean change from baseline in FPG was -2.4 mmol/l (-42.9 mg/dl) for metformin compared with +1.2 mmol/l (+21.4 mg/dl) for placebo (P < 0.001). Mean HbA(1c) values, adjusted for baseline levels, were also significantly lower for metformin compared with placebo (7.5 vs. 8.6%, respectively; P < 0.001). Improvement in FPG was seen in both sexes and in all race subgroups. Metformin did not have a negative impact on body weight or lipid profile. Adverse events were similar to those reported in adults treated with metformin. CONCLUSION: Metformin was shown to be safe and effective for treatment of type 2 diabetes in pediatric patients.     

Rosiglitazone may reduce thyroid cancer risk in patients with type 2 diabetes

Abstract

Background. Whether rosiglitazone use in patients with type 2 diabetes may affect thyroid cancer risk has not been investigated.

Methods. The reimbursement databases of all diabetic patients under oral anti-diabetic agents or insulin from 1996 to 2009 were retrieved from the National Health Insurance of Taiwan. An entry date was set at 1 January 2006, and 887,665 patients with type 2 diabetes were followed for thyroid cancer incidence until the end of 2009 for ever-users, never-users, and subgroups of rosiglitazone exposure using tertile cut-offs for time since starting rosiglitazone, duration of therapy, and cumulative dose. Hazard ratios were estimated by Cox regression.

Results. There were 103,224 ever-users and 784,441 never-users, with respective numbers of incident thyroid cancer of 84 (0.08%) and 764 (0.10%), and respective incidence of 23.12 and 28.09 per 100,000 person-years. The overall multivariable-adjusted hazard ratio was not significant. However, in dose-response analyses, the adjusted hazard ratios (95% confidence intervals) were significant for the third tertile of duration of therapy (≥ 14 months) and cumulative dose (≥ 1,800 mg) for age ≥ 50 years: 0.53 (0.31–0.89) and 0.50 (0.29–0.87), respectively.

Conclusions. This study suggests that rosiglitazone use in patients with type 2 diabetes may reduce the risk of thyroid cancer.     

Repaglinide versus metformin in combination with bedtime NPH insulin in patients with type 2 diabetes established on insulin/metformin combination therapy

OBJECTIVE: To compare the effect on glycemic control and weight gain of repaglinide versus metformin combined with bedtime NPH insulin in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 80 subjects treated with 850 or 1,000 mg t.i.d. metformin combined with bedtime NPH insulin were randomized to 13 weeks of open-label treatment with 4 mg t.i.d. repaglinide (n = 39) or metformin (dose unchanged) (n = 41). Insulin dose was titrated at the clinician's discretion, aiming for a fasting blood glucose (FBG) < or =6.0 mmol/l. RESULTS: Baseline age, diabetes duration, insulin requirement, weight, BMI, FBG, and HbA(1c) (Diabetes Control and Complications Trial-aligned assay, normal range 4.6-6.2%) were similar. Glycemic control improved (nonsignificantly) with insulin/metformin by (mean) 0.4%, from 8.4 to 8.1% (P = 0.09) but deteriorated with insulin/repaglinide by (mean) 0.4%, from 8.1 to 8.6% (P = 0.03; P = 0.005 between groups). Weight gain was less with insulin/metformin: 0.9 +/- 0.4 kg (means +/- SE) (P = 0.01) versus 2.7 +/- 0.4 kg (P < 0.0001) (P = 0.002 between groups). The Diabetes Treatment Satisfaction Questionnaire score (potential range 0 [minimum] to 36 [maximum]) increased from 32.4 +/- 0.8 to 34.1 +/- 0.5 (P = 0.01) with insulin/metformin but decreased from 32.5 +/- 0.9 to 29.1 +/- 1.3 (P < 0.002) with insulin/repaglinide. CONCLUSIONS: Combined with bedtime NPH insulin, metformin provides superior glycemic control to repaglinide with less weight gain and improved diabetes treatment satisfaction.     

Efficacy of low-dose metformin in Japanese patients with type 2 diabetes mellitus

The goal of this study was to examine the antihyperglycemic effect of low-dose metformin in nonobese and obese Japanese patients with type 2 diabetes mellitus. After 3 months of reeducation and stabilization of diet therapy (25 kcal/kg of ideal body weight), metformin treatment was initiated. We administered metformin (500 to 750 mg daily) as monotherapy (n = 11) or in combination with a sulfonylurea (n = 14). After 6 months of treatment, the fasting plasma glucose level (mean ± SD) decreased from 190 ± 42 mg/dL to 155 ± 37 mg/dL and the glycated hemoglobin A_1c level (mean ± SD) from 8.8 ± 1.2% to 7.4 ± 1.0% in the monotherapy group. These same variables decreased from 218 ± 60 mg/dL to 162 ± 30 mg/dL and from 9.5 ± 1.2% to 8.4 ± 1.2% in the combination therapy group. All of these changes were statistically significant. Our results demonstrate that even low doses of metformin can improve hyperglycemia in Japanese patients with type 2 diabetes mellitus.     

Role of gut microbiome in regulating the effectiveness of metformin in reducing colorectal cancer in type 2 diabetes

The prevalence of colorectal cancer (CRC) and type 2 diabetes mellitus (T2DM) is increasing globally. It is rarely noticed that the incidence of CRC is higher in patients with T2DM. What needs to be mentioned is that metformin, a commonly used clinical drug for T2DM, attracts scholars’ attention because of its benefits in lowering the risk of developing CRC. Hence, we try to find the common grounds of initiation of T2DM and CRC and the reason why metformin reduces the risk of CRC in patients with T2DM. We noticed consistent changes of gut microbiota, such as elevated Bacteroides, Prevotella and Bifidobacterium and depressed Firmicutes and Lactobacillus. Furthermore, many studies in recent years have proved that the efficacy of metformin, such as improving blood glucose, depends on the gut microbiota. Coincidentally, the progression of CRC is inseparable from the contributions of gut microbiota. Therefore, we first proposed the concept of the metformin-gut microbiota–CRC (in T2DM) axis to explain the effect of metformin in reducing CRC in patients with T2DM. In this review, we elaborated the new concept and its potential clinical application value.     

Effects of exercise on cardiovascular risk factors in type 2 diabetes: a meta-analysis

OBJECTIVE

Exercise is a cornerstone of diabetes management and the prevention of incident diabetes. However, the impact of the mode of exercise on cardiovascular (CV) risk factors in type 2 diabetes is unclear.

RESEARCH DESIGN AND METHODS

We conducted a systematic review of the literature between 1970 and October 2009 in representative databases for the effect of aerobic or resistance exercise training on clinical markers of CV risk, including glycemic control, dyslipidemia, blood pressure, and body composition in patients with type 2 diabetes.

RESULTS

Of 645 articles retrieved, 34 met our inclusion criteria; most investigated aerobic exercise alone, and 10 reported combined exercise training. Aerobic alone or combined with resistance training (RT) significantly improved HbA_1c −0.6 and −0.67%, respectively (95% CI −0.98 to −0.27 and −0.93 to −0.40, respectively), systolic blood pressure (SBP) −6.08 and −3.59 mmHg, respectively (95% CI −10.79 to −1.36 and −6.93 to −0.24, respectively), and triglycerides −0.3 mmol/L (95% CI −0.48 to −0.11 and −0.57 to −0.02, respectively). Waist circumference was significantly improved −3.1 cm (95% CI −10.3 to −1.2) with combined aerobic and resistance exercise, although fewer studies and more heterogeneity of the responses were observed in the latter two markers. Resistance exercise alone or combined with any other form of exercise was not found to have any significant effect on CV markers.

CONCLUSIONS

Aerobic exercise alone or combined with RT improves glycemic control, SBP, triglycerides, and waist circumference. The impact of resistance exercise alone on CV risk markers in type 2 diabetes remains unclear.Diabetes is a chronic condition brought about by the body’s inability to produce enough insulin or to use the insulin that it produces. As a result of this insulin insufficiency, there is an increase in the concentration of glucose in the blood (known as hyperglycemia), as well as other metabolic abnormalities. According to the World Health Organization, the number of individuals with diabetes worldwide has increased from 30 million in 1985 to 171 million in 2000 (1); these rates are expected to further increase, with the World Health Organization predicting that the worldwide prevalence in adults will reach 6.4% by 2030, corresponding to a 39% increase from 2000 to 2030 (2). Of the diagnosed cases of diabetes, it is estimated that approximately 90–95% of individuals have type 2 diabetes (3).Type 2 diabetes is an independent risk factor for both macrovascular disease (e.g., myocardial infarction and stroke) and microvascular disease (e.g., retinopathy and nephropathy), and is often associated with other cardiovascular (CV) disease (CVD) risk factors, including high blood pressure (BP), dyslipidemia, obesity, lack of physical activity, and smoking (4,5). Although glycemic control is a key therapeutic target for individuals with type 2 diabetes, the major cause of morbidity and mortality among this patient population is CVD, not metabolic dysregulation (6). CVD is the leading cause of mortality among individuals with diabetes (7,8), accounting for 65% of all deaths among this patient group (9). Furthermore, diabetes is twice as common among populations of patients with heart failure when compared with matched control subjects (10), and patients with diabetes are more likely to develop heart failure after a myocardial infarction than nondiabetic individuals (11).Exercise has long been recognized as a cornerstone of diabetic management and the prevention of incident diabetes. For example, the American College of Sports Medicine currently recommends that individuals with type 2 diabetes expend a minimum cumulative total of 1,000 kcal per week of energy from physical activities (12). Meta-analyses have shown that aerobic or resistance training (RT) is related to statistically significant improvements in glycemic control (13–15). Support for the effect of exercise on other CV risk factors, however, is lacking. Therefore, we conducted this review to investigate the effects of aerobic exercise, RT, and combined aerobic and RT on CV risk factors in type 2 diabetes.     

XRCC2 Arg188His polymorphism and colorectal cancer risk: a meta-analysis

ObjectiveTo investigate the potential correlation between the Arg188His (rs3218536) polymorphism of X-ray repair cross-complementing 2 (XRCC2) and colorectal cancer (CRC) risk, as the association remains unclear.MethodsThe CNKI, PubMed, EMBASE and Cochrane library databases were systematically searched for relevant studies published up to July 2021. Data were extracted from included studies, and analysed for pooled or subgroup odds ratios (ORs) with 95% confidence intervals (CIs) using STATA 12.0 software.ResultsSeven published studies were included. Pooled analysis revealed that the XRCC2 Arg188His polymorphism was associated with increased CRC risk (His versus Arg: OR 1.14, 95% CI 1.01, 1.29). Trial Sequential Analysis to test the power of the results showed that they were unreliable and the meta-analysis required additional studies.ConclusionThe current meta-analysis suggests that the XRCC2 Arg188His polymorphism may be a risk factor for CRC.     

The metabolic effects of once daily extended-release metformin in patients with type 2 diabetes: a multicentre study

Aim: To investigate the effects of extended‐release metformin (MXR) compared with immediate‐release metformin (MIR) on post‐prandial glycaemic excursion, chronic glycaemia, lipid profiles, insulin resistance and islet function in type 2 diabetes. Methods: A randomised, open‐labelled, positive‐controlled multicentre study was conducted on 150 Chinese patients with type 2 diabetes. After 2 weeks of run‐in period with MIR, 150 subjects were randomised into MXR group and MIR group. The patients in MXR group were assigned to take MXR 1500 mg once daily after dinner, while the patients in MIR group were assigned to continue MIR 500 mg thrice daily after meals for 12 weeks. Standard meal tests were carried out at baseline and at the end of this study. Plasma glucose, serum insulin, HbA1c and lipid profiles were measured. Homeostasis model assessment (HOMA) was used to evaluate insulin resistance index (HOMA‐IR) and islet β‐cell function index (HOMA‐B). Results: Either MIR or MXR modestly, but significantly decreased HbA1c levels and body mass index (BMI) after 12 weeks of treatment. However, there were no significant differences between two groups. The post‐prandial glycaemia at 120 min after a standard meal in MXR group was higher than in MIR group (11.02 ± 3.08 mmol/l vs. 9.74 ± 2.61 mmol/l, p < 0.05). Moreover, no differences in the areas under curve of insulin release response, HOMA‐B, HOMA‐IR and lipid profiles were found within or between groups after 12 weeks of treatment. Conclusion: The effects of once daily MXR on chronic glycaemia, BMI, lipid profiles, insulin resistance and islet function are comparable with that of thrice daily MIR in oriental population.