Economic evaluation of therapeutic interventions to prevent Type 2 diabetes in Canada.

AIMS: To compare the health and economic outcomes of using acarbose, an intensive lifestyle modification programme, metformin or no intervention to prevent progression to diabetes in Canadian individuals with impaired glucose tolerance (IGT). METHODS: A model was developed to simulate the course of individuals with IGT under each treatment strategy. Patients remain in the IGT state or transition from IGT to diabetes, to normal glucose tolerance (NGT) or to death. Effectiveness and resource use data were derived from published intervention trials. A comprehensive health-care payer perspective incorporating all major direct costs, reported in 2000 Canadian dollars, was adopted. RESULTS: Over a decade, 70 of the 1000 untreated patients are expected to die and 542 develop diabetes. Intensive lifestyle modification is estimated to prevent 117 cases of diabetes, while metformin would prevent 52 and acarbose 74 cases. The proportion of those who return to NGT also increases with any treatment. While lifestyle modification is more effective, it can increase overall costs depending on how it is implemented, whereas acarbose and metformin reduce costs by nearly $1000 per patient. Lifestyle modification was cost effective, varying from CAD $10 000/LYG vs. acarbose. Acarbose costs somewhat more than metformin, but is more effective: CAD $1798/LYG. CONCLUSION: The results of this model suggest that the treatment of IGT in Canada is a cost-effective way to prevent diabetes and may generate savings. While pharmacological treatments tended to be less costly, intensive lifestyle modification, if maintained, led to the greatest health benefits at reasonable incremental costs.     

对中高危高血压患者葡萄糖耐量试验异常的干预研究

目的观察对葡萄糖耐量试验异常的中高危高血压患者进行干预12个月后血压及糖代谢的情况。方法对213例葡萄糖耐量减低（IGT）的高血压患者随机分为生活方式控制组（LC）、生活方式控制加二甲双胍组（LC＋M）、生活方式控制加阿卡波糖组（LC＋A）三组,分析干预12个月后各组IGT转化为正常葡萄糖耐量（NGT）和新发糖尿病（DM）的发生率以及血压与IGT、NGT、DM之间的关系。结果三组干预12个月后,2hPG均明显降低（P〈0．01）,与LC组比,LC＋M组和LC＋A组转为NGT的人数均明显增多（P〈0．01）,LC＋M组和LC＋A组相比,在转为NGT和DM的人数方面差异无统计学意义（P〉0．05）,且血压越达标,糖尿病发生率越低。结论对糖耐量异常的高血压患者,积极的进行干预,可以减少糖尿病的发生,生活方式控制加药物治疗优于单纯生活方式控制。     

Targeting the consequences of the metabolic syndrome in the diabetes prevention program

This review describes the effect of lifestyle change or metformin compared with standard care on incident type 2 diabetes and cardiometabolic risk factors in the Diabetes Prevention Program and its Outcome Study. The Diabetes Prevention Program was a randomized controlled clinical trial of intensive lifestyle and metformin treatments versus standard care in 3234 subjects at high risk for type 2 diabetes. At baseline, hypertension was present in 28% of subjects, and 53% had metabolic syndrome with considerable variation in risk factors by age, sex, and race. Over 2.8 years, type 2 diabetes incidence fell by 58% and 31% in the lifestyle and metformin groups, respectively, and metabolic syndrome prevalence fell by one-third with lifestyle change but was not reduced by metformin. In placebo- and metformin-treated subjects, the prevalence of hypertension and dyslipidemia increased during the Diabetes Prevention Program, whereas lifestyle intervention slowed these increases significantly. During long-term follow-up using modified interventions, type 2 diabetes incidence decreased to ≈5% per year in all groups. This was accompanied by significant improvement in cardiovascular disease risk factors over time in all treatment groups, in part associated with increasing use of lipid-lowering and antihypertensive medications. Thus a program of lifestyle change significantly reduced type 2 diabetes incidence and metabolic syndrome prevalence in subjects at high risk for type 2 diabetes. Metformin had more modest effects.     

Effect of Acarbose on Vascular Disease in Patients with Abnormal Glucose Tolerance

INTRODUCTION: Excessive postprandial (pp) glucose excursion in people with IGT and type 2 diabetes is associated with a cascade of proatherogenic events. Acarbose, a potent competitive inhibitor of alpha-glucosidases of the small intestine specifically reduces pp hyperglycemia with an average reduction of HbA1c by 0.8% in Cochrane metaanalysis. This is associated with pleiotropic effects on a broad spectrum of cardiovascular (CV) risk factors: reduction of overweight, lowering of blood pressure, triglycerides, hsCRP, fibrinogen and other biomarkers of low grade inflammation. RESULTS AND DISCUSSION: Flow mediated vasodilation was improved and progression of intima media thickness was reduced by acarbose. In the STOP-NIDDM trial in people with IGT acarbose decreased the incidence of diabetes by 36%. The STOP-NIDDM trial with CV events as secondary objective is the only intervention trial in people with IGT so far with a significant benefit for CV disease inclusive hypertension. In a metaanalysis of controlled studies (MeRIA) in patients with type 2 diabetes, treatment with acarbose was associated with a 64% lower rate of myocardial infarction and 35% less CV events. CONCLUSION: Thus results so far available prove that acarbose is an effective and safe drug to treat abnormal glucose tolerance. They suggest that acarbose can help to control a broad spectrum of CV risk factors and may prevent CV disease.     

Preventing Type 2 diabetes and the dysmetabolic syndrome in the real world: a realistic view.

The last two decades have seen an explosive increase in the number of people with diabetes globally. There is now an urgent need for strategies to prevent the emerging global epidemic. Several recent successful intervention studies, both lifestyle and pharmacological, targeting subjects with impaired glucose tolerance (IGT) have stimulated enthusiasm for prevention of Type 2 diabetes. Lifestyle interventions reduced the incidence of diabetes by over 50% in the Finnish Diabetes Prevention Study and the Diabetes Prevention Program. Can the findings of these two studies be applied globally? Underpinning the enthusiasm, there needs to be a realistic approach to interventions in both developed and developing nations, and in ethnic groups where a better understanding of the socio‐economic, cultural and demographic issues and perceptions surrounding chronic diseases such as diabetes is required. Whether the strategies used in these two studies can be translated into a ‘real world’ scenario is doubtful. In practice, it is more than likely that a number of strategies will be needed to compliment the lifestyle approach. These will include pharmacological approaches with metformin, acarbose and other agents used to treat diabetes and its complications, currently under investigation. Longer‐term follow‐up studies will also clarify whether both lifestyle and pharmacological interventions actually prevent Type 2 diabetes, or merely delay its onset.     

The prevention of type 2 diabetes: what is the evidence?

The prevalence of diabetes is increasing in epidemic proportion worldwide. Because of the morbidity and mortality associated with the disease, it is becoming a major burden for the health care system. With a better understanding of the pathogenesis of type 2 diabetes, the concept of primary prevention has emerged. A number of studies demonstrated that both lifestyle modification program and pharmacological interventions in subjects with impaired glucose tolerance (IGT) can prevent or delay the progression to diabetes. The Diabetes Prevention Study (DPS) and the Diabetes Prevention Program (DPP) convincingly showed that an intensive lifestyle modification program is highly effective in decreasing the risk of diabetes in a high risk population (risk reduction of 58%). Four other smaller studies have made similar observations. The DPP study showed that metformin can reduced the risk of diabetes by 31% in subjects with IGT. The STOP-NIDDM trial confirmed the efficacy of acarbose in decreasing the risk of diabetes by 36% in similar high risk population. The TRIPOD study showed that troglitazone can reduce the incidence of diabetes by 55% in Hispanic women with a history of gestational diabetes. And more recently, the XENDOS study showed that in very obese population on intensive lifestyle modification program, xenical treatment was associated with a 37% reduced incidence of diabetes compared to placebo. Three studies suggested that bariatric surgery in morbidly obese subjects with or without IGT can reduce the incidence of diabetes to near zero. Eight of 10 studies showed that treatment with inhibitors of the renin-angiotensin aldosterone system in high risk population for cardiovascular disease (CVD) were associated with a significant reduction in the subsequent development of diabetes as a secondary outcome. The WOSCOPS study and the HERS study examined the effect of pravastatin and estrogen/progestin respectively on cardiovascular events and observed that these pharmacological interventions were associated with a 30% and 35% reduction in the incidence of diabetes as secondary outcome. There are 3 major trials currently in progress examining the effect of rosiglitazone/ramipril (the DREAM study), nateglinide/valsartan (the NAVIGATOR study) and pioglitazone (the ACT NOW study) on the development of diabetes in IGT subjects as a primary outcome. We also have 3 studies studying the prevention of diabetes as secondary outcomes: the ONTARGET-TRANSCEND study examining telmisartan with or without ramipril, and the ORIGIN study testing glargine insulin/omega 3. The evidence is overwelming-diabetes can be prevented or delayed in high risk population through lifestyle modification or pharmacological interventions. This new information now has to be translated in the real world into well defined strategies for screening and treating high risk population. Prevention of the disease is our only chance to alleviate the ever growing burden of diabetes mellitus in the world.     

Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions

CONTEXT: A past history of gestational diabetes mellitus (GDM) confers a very high risk of postpartum development of diabetes, particularly type 2 diabetes. OBJECTIVE: The Diabetes Prevention Program (DPP) sought to identify individuals with impaired glucose tolerance (IGT) and intervene in an effort to prevent or delay their progression to diabetes. This analysis examined the differences between women enrolled in DPP with and without a reported history of GDM. DESIGN: The DPP was a randomized, controlled clinical trial. SETTING: The study was a multicenter, National Institutes of Health-sponsored trial carried out at 27 centers including academic and Indian Health Services sites. Patients: A total of 2190 women were randomized into the DPP and provided information for past history of GDM. This analysis addressed the differences between those 350 women providing a past history of GDM and those 1416 women with a previous live birth but no history of GDM. INTERVENTIONS: Subjects were randomized to either standard lifestyle and placebo or metformin therapy or to an intensive lifestyle intervention. MAIN OUTCOMES: The primary outcome was the time to development of diabetes ascertained by semiannual fasting plasma glucose and annual oral glucose tolerance testing. Assessments of insulin secretion and insulin sensitivity were also performed. RESULTS: Whereas entering the study with similar glucose levels, women with a history of GDM randomized to placebo had a crude incidence rate of diabetes 71% higher than that of women without such a history. Among women reporting a history of GDM, both intensive lifestyle and metformin therapy reduced the incidence of diabetes by approximately 50% compared with the placebo group, whereas this reduction was 49 and 14%, respectively in parous women without GDM. These data suggest that metformin may be more effective in women with a GDM history as compared with those without. CONCLUSIONS: Progression to diabetes is more common in women with a history of GDM compared with those without GDM history despite equivalent degrees of IGT at baseline. Both intensive lifestyle and metformin are highly effective in delaying or preventing diabetes in women with IGT and a history of GDM.     

Primary prevention of diabetes mellitus type 2

The increasing incidence of type 2 diabetes constitutes a considerable individual and socio-economic risk, therefore preventive concepts are urgently needed. Three prospective studies show that a "life-style-intervention" as well as drugs can prevent the development of diabetes as well as cardiovascular complications: The Diabetes Prevention Study (DPS) evaluated the influence of a "life-style-intervention". The Diabetes Prevention Program (DPP) additionally examined the effect of metformin. In the STOP-NIDDM-Study acarbose was used for diabetes prevention and cardiovascular endpoints were also evaluated. The incidence of type 2 diabetes can be significantly reduced by a "life-style-intervention" and also by the administration of metformin or acarbose. With acarbose cardiovascular events are reduced significantly and comparably to a therapy with statins in primary prevention.     

Impaired Glucose Tolerance

Impaired glucose tolerance (IGT) is determined by measuring plasma glucose levels 2 hours after glucose loading in the oral glucose tolerance test. There is good evidence from epidemiologic and prospective trials [e.g. Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Europe (DECODE)] linking IGT with the development of type 2 diabetes mellitus and cardiovascular disease (CVD). IGT is characterized by an increase in postprandial glucose levels, which is considered the earliest metabolic abnormality in type 2 diabetes mellitus. It is one of a series of risk factors for CVD (hypertension, high triglyceride levels, low high-density lipoprotein-cholesterol and central obesity), known as the metabolic syndrome. The different factors making up this syndrome are intimately related. An impaired lipid profile can contribute to insulin resistance, as IGT may play a pathogenic role on other cardiovascular risk factors. IGT is the first easily identifiable step in the pathophysiology of type 2 diabetes mellitus. It is associated with high risk for type 2 diabetes mellitus and subsequent vascular morbidity and mortality. It is currently unknown whether treating IGT will reduce the incidence of macrovascular complications, as studies addressing this issue have yet to be conducted. Therefore, the main reason to identify and treat IGT is to prevent or delay the onset of type 2 diabetes mellitus. It has been demonstrated that lifestyle intervention with diet and exercise can reduce the incidence of type 2 diabetes mellitus. Pharmacologic intervention with metformin and acarbose is also effective. Other drugs, such as those indicated to treat other parameters of the metabolic syndrome, may also be useful. We can now be assured that prevention or delay of onset of type 2 diabetes mellitus is possible in individuals with IGT, either by changes in lifestyle or by pharmacotherapy.     

Comparison of the effects of pioglitazone and metformin on insulin resistance and hormonal markers in patients with impaired glucose tolerance and early diabetes.

Impaired glucose tolerance (IGT) is associated with cardiovascular risk factors, but the effects of pioglitazone and metformin on IGT are not well described. We tested the hypothesis that each drug would exhibit antiatherogenic and anti-inflammatory effects in subjects with IGT and early diabetes. The study design was a prospective, randomized, open label, cross-over study. Blood tests, including a 75-g oral glucose tolerance test (OGTT), were performed at baseline and after each treatment. Pioglitazone 15 mg/day or metformin 500-750 mg/day was given for 3 months. Biochemical markers to assess insulin resistance as well as lipid, inflammatory, neurohumoral, and hemostatic factors were included. Twenty-five subjects (17 male, 8 female; age [mean+/-SD]: 61+/-9 years; 84% hypertensive) completed the protocol. Of 25 subjects, 14 were diagnosed as IGT and 11 as diabetes with 75-g OGTT. Pioglitazone significantly reduced fasting glucose (p<0.05), and homeostasis model assessment of insulin resistance (HOMA-IR) (p<0.05) and metformin (p<0.01) reduced cholesterol. Both drugs significantly reduced aldosterone (both p<0.05) and von Willebrand factor (vWF) (both p<0.05). Plasma adiponectin was increased only by pioglitazone (p<0.001). Neither drug affected BP levels. In conclusion, pioglitazone was superior to metformin for the improvement of insulin resistance and adiponectin, and both drugs were equally effective in reducing vWF and aldosterone in subjects with IGT and early diabetes. Early intervention with pioglitazone or metformin therapy may reduce the incidence of future cardiovascular disease in subjects with impaired glucose tolerance or early diabetes.     

综合干预对老年糖调节异常患者的影响

目的分析综合干预对老年血糖调节异常(IGR)患者进展为糖尿病的情况。方法对177例老年IGR患者(干预组)的生活方式进行4年综合干预,同期选择55例不进行综合干预的IGR患者作为对照组,分析空腹血糖受损、糖耐量异常患者进展为糖尿病的情况。结果干预组患者空腹血糖受损、糖耐量异常、空腹血糖受损合并糖耐量异常进展为糖尿病的比率分别为17.14%、20.99%和42.31%,空腹血糖受损合并糖耐量异常进展为糖尿病的比率分别是空腹血糖受损、糖耐量异常的2.47、2.02倍。与对照组比较,干预组空腹血糖受损、糖耐量异常患者进展为糖尿病的比率分别减少了55.01%和52.77%(P0.05,P0.01)。结论综合干预能有效控制与消弱心血管疾病危险因素,阻止或延缓IGR患者进展为糖尿病。     

Association of the Leu72Met polymorphism of the ghrelin gene with the risk of Type 2 diabetes in subjects with impaired glucose tolerance in the Finnish Diabetes Prevention Study.

AIMS: Ghrelin is a gut-brain regulatory peptide stimulating appetite and controlling energy balance. In previous studies, the Leu72Met polymorphism of the ghrelin gene has been associated with obesity and impaired insulin secretion. We investigated whether the Leu72Met polymorphism is associated with the incidence of Type 2 diabetes in subjects with impaired glucose tolerance (IGT) participating in the Finnish Diabetes Prevention Study (DPS). METHODS: DPS was a longitudinal intervention study carried out in five participating centres in Finland. A total of 522 subjects with IGT were randomized into either an intervention or a control group and DNA was available from 507 subjects. The Leu72Met polymorphism was screened by the restriction fragment length polymorphism method. RESULTS: There were no differences in clinical and anthropometric characteristics among the genotypes at baseline. IGT subjects with the Met72 allele were at higher risk of developing Type 2 diabetes than subjects with the Leu72Leu genotype (P = 0.046). Our data also demonstrated that IGT subjects with the common Leu72Leu genotype developed Type 2 diabetes less frequently under intervention circumstances than subjects with the Met72 allele (OR = 0.28, 95% CI 0.10-0.79; P = 0.016). CONCLUSIONS: Subjects with the Leu72Leu genotype had a lower risk for the development of Type 2 diabetes. This was observed particularly in the study subjects who underwent an intensive diet and exercise intervention. Defective first-phase insulin secretion related to the Met72 allele might be one factor contributing to the conversion to Type 2 diabetes.     

Perspectives of the use of antihyperglycemic preparations in patients with metabolic syndrome and prediabetes

The state of prediabetes comprises two types of impairment of carbohydrate metabolism: impaired fasting glycemia and impaired glucose tolerance. According to International Diabetes Federation at present number of patients with prediabtes is almost 2 times greater than that of patients with diabetes. Risk of development of diabetes and cardiovascular complications in patients with prediabtes is 2 times higher than in persons with normal blood glucose level. Impaired glucose tolerance is also one of main components of metabolic syndrome. For prevention of risk of development of diabetes and cardiovascular complications besides life style changes it is necessary to influence insulin resistance and normalize carbohydrate metabolism. When life style changes are ineffective the use of antihyperglycemic drugs is essential. Antihyperglycemic preparations metformin, acarbose, thiazolidinediones do not affect function of pancreatic b-cells and do not cause hypoglycaemia. This allows to use these drugs in patients without diabetes but having insulin resistance and prediabetes. Therapeutic effect of metformin and rosiglitazone is related to improvement of sensitivity to insulin in insulin dependent tissues, suppression of glyconeogenesis in the liver, and enhancement of pancreatic b-cells function. Action of acarbose is based on local inhibition of intestinal enzyme a-glycosidase, what leads to diminishment of postprandial hyperglycemia peak. Results of DPP, STOP-NIDDM and DREAM trials have demonstrated high efficacy of antihyperglycemic preparations in prevention of type 2 diabetes.     

The prevention of type 2 diabetes--lifestyle change or pharmacotherapy? A challenge for the 21st century

Diabetes mellitus is occurring in epidemic proportions in many countries. In Australia 7.4% of people over 25 years of age have diabetes (mostly type 2) and comparable or higher prevalences have been reported in the United States and a number of Asian countries. The enormous economic and social cost of this disease makes a compelling case for prevention. Epidemiological studies have shown clearly that type 2 diabetes results from an interaction between a genetic predisposition and lifestyle factors including obesity, sedentary behaviour and both calorie excess and various dietary constituents. The natural history of type 2 diabetes includes a preceding period of impaired glucose tolerance (IGT)/impaired fasting glucose (IFG) which provides an opportunity for targeted intervention within large communities. Lifestyle intervention studies have consistently shown that quite modest changes can reduce the progression from IGT to diabetes by 50-60%. It may, however, not be possible to translate these successful findings to larger cohorts or maintain the lifestyle changes longer term. This has lead to consideration of pharmacotherapy. While small studies with sulphonylureas are inconclusive, benefits have been found for metformin, acarbose and troglitazone. Big intervention studies with ramipril, rosiglitazone, valsartan and nateglinide are underway. Pharmacological intervention raises a whole range of ethical, economic and practical issues not the least of which is the problem of long term therapy of the 'otherwise well'.     

预防心血管终点事件,从关注糖耐量受损开始

糖尿病患者常合并心血管疾病,预防心血管事件是糖尿病患者治疗的主要目的 之一.目前针对糖尿病患者进行强化血糖干预的临床试验表明,晚期血糖干预心血管获益不明显.研究发现,绝大部分2型糖尿病患者在诊断时已经存在明确的动脉粥样硬化,甚至在糖耐量受损(IGT)阶段大血管病变就已经存在.这提示IGT可能是血糖干预以获终点收益的最佳时机.     

葡萄糖耐量受损需要干预吗？

葡萄糖耐量受损（IGT）是最主要的糖调节异常,在糖尿病前期人群中占有较大的比例。IGT人群是2型糖尿病最重要和最需要重点关注的高危人群,如果不进行积极有效的干预,每年有10％～15％的IGT患者会进展为2型糖尿病。如进行积极干预,则可以延缓这一进程,甚至实现逆转。IGT人群也是心血管疾病的高危人群,来自临床的数据表明,IGT人群罹患各种心血管疾病的风险要显著高于糖代谢正常的正常人群。因此,对于IGT人群,必须给予积极和有效的干预,从而达到预防糖尿病和减低心血管事件风险的目的。干预IGT,首选生活方式干预,当单独采取生活方式干预无法达到预期目标时,可采取药物干预措施。     

Prevention of Type 2 diabetes mellitus. A review of the evidence and its application in a UK setting.

Abstract Type 2 Diabetes mellitus (T2DM) is a complex metabolic, multifactorial disease, which affects the quality, quantity and style of life. People with T2DM have a life expectancy that can be shortened by as much as 15 years, with up to 75% dying of macrovascular complications. To reduce the impact of T2DM in the 21st century, we need an approach that not only optimally treats the person with established diabetes but also prevents diabetes from occurring in the first place. The best evidence for prevention of diabetes is for interventions that target individuals at highest risk. Targeting patients who have impaired glucose tolerance with lifestyle changes including physical activity and dietary factors has been shown to be effective in the Chinese, North American and Finnish populations. In order for such lifestyle interventions to be successful in other populations, they need to be culturally sensitive, individualized and sustained. Some pharmacological agents including metformin and acarbose have also been shown to be effective, although the profile of those who respond is different. There continues to be a need to develop and evaluate interventions that target communities and populations at risk in a UK setting.     

二甲双胍和食物纤维在糖耐量低减人群向2型糖尿病发展中的干预作用

目的　观察二甲双胍和食物纤维预防糖耐量低减 (IGT)人群进展为 2型糖尿病 (DM)的作用。　方法　以口服 75 g葡萄糖耐量试验 (OGTT)确诊 (WHO标准 )的 IGT2 93例中男 2 16例 ,女 77例。入选者年龄 35岁以上 ,体重指数 (BMI)在 19kg/ m2以上。随机分为对照组 72例 ,教育组 5 7例 ,食物纤维组 84例 ,二甲双胍组 80例。对照组进行一般的健康教育 ;教育组进行饮食指导 ,每半年1次 ;食物纤维组除健康教育外 ,每日口服食物纤维 12 g;二甲双胍组每日口服二甲双胍 0 .75 g,分 3次餐后口服。对四组参试者每半年作 1次 OGTT,同时测身高、体重、BMI、12 h尿白蛋白 ,复查日当天不服干预药物或食物纤维。共观察 3年。若 2次 OGTT或最后 1次复查结果为 DM,则判断为已发展为 DM。　结果　 2 93例 IGT在观察中有 2 3例 (7.8% )退出。空腹血糖 (FBS)和服糖后 1h血糖 (1hPBS)在对照组、教育组和食物纤维组均较治疗前略有升高 ,但在二甲双胍治疗组均有下降。四组间FBS比较 F=8.118,P<0 .0 1,四组间 1h PBS比较 F=3.6 97,P=0 .0 12。观察期末对照组 16例 (2 5 .0 % )、教育组 11例 (2 1.6 % )、食物纤维组 13例 (16 .3% )、二甲双胍组 7例 (9.3% )转化为 DM,二甲双胍组在治疗后 DM转化率明显低于对照组 (χ2 =6 .318,P<0 .0     

Cost and clinical implications of diabetes prevention in an Australian setting: a long-term modeling analysis

Aims/hypothesisMetformin and intensive lifestyle changes (ILC) reduced the incidence of type 2 diabetes (T2D) versus standard care (control) in overweight or obese subjects with impaired glucose tolerance (IGT) in the Diabetes Prevention Program (DPP) trial and Diabetes Prevention Program Outcomes Study (DPPOS). We projected lifetime clinical and economic outcomes based on the results from the DPP + DPPOS, from a 3rd-party payer perspective in Australia.MethodsA semi-Markov, 2nd-order Monte Carlo model was developed with four health states: “normal glucose regulation” (NGR); IGT; T2D and ‘dead’. Outcomes were discounted at 5% annually. Univariate and probabilistic sensitivity analyses were performed. Incremental cost-effectiveness ratios (ICERs) were calculated.ResultsCumulative incidence (standard deviation) of T2D was 89.7% (0.2), 83.8% (0.2) and 73.4% (0.3%) for control, metformin and ILC respectively. Lifetime incremental direct costs were $1217 (4411) per subject for metformin versus control, with cost savings of $289 (4296) for ILC versus control. ILC therefore dominated control, with improvements in clinical outcomes and overall cost savings. Incremental costs per QALY-gained for metformin versus control were $10,142. Probability of cost-effectiveness at willingness-to-pay threshold of $50,000 was 78% and 100% for metformin or ILC respectively. Results were most sensitive to probabilities of developing T2D and costs of implementing the interventions.Conclusions/interpretationSubstantial improvements in lifetime clinical outcomes could be expected in high risk subjects treated with metformin or ILC. Prevention of T2D in this group of subjects is good value for money, and may even lead to long term cost savings.     

Metabolic syndrome does not increase the risk of conversion of impaired glucose tolerance to diabetes in Asian Indians--Result of Indian diabetes prevention programme

AIMS: In this study, we assessed for the prevalence of metabolic syndrome (MetS) in the cohort of subjects with impaired glucose tolerance (IGT) in the Indian Diabetes Prevention Programme and studied whether the syndrome enhanced the conversion to diabetes. METHODS: Effectiveness of lifestyle modification (LSM), metformin (Met) and LSM plus Met was tested in a randomised, controlled primary prevention study in subjects with IGT n=502 (M:W 397:105) at a median follow up of 30 months. Baseline prevalence of MetS was calculated using the WHO criteria. Insulin resistance (IR) was calculated using homeostasis model assessment (HOMA) method. RESULTS: MetS was present in 233 subjects (46.4%; 95% CI 41.9-50.9) in the total group, in men (n=168; 42.3%; 95% CI 37.4-47.3) and in women (n=65; 61.9%; 95% CI 51.9-71.2) (men versus women chi(2)=12.8, p=0.0005). Insulin resistance (HOMA-IR>or=4.1) was present in 69.1% with no gender difference. IR increased proportionately with increasing number of abnormalities, in IGT (39.8%), IGT plus one abnormality (56.5%) and IGT plus any two or more abnormalities (69.1%) (Mantel Haenszel chi(2)=22.8, p<0.0001). Incidence of diabetes was similar in subjects with (40.3%) (n=94/233) or without (40.1%) (n=108/269) MetS (p=0.97). Cox's regression analysis confirmed that MetS did not enhance the conversion rate of IGT to diabetes both in the control (HR=0.88, 95% CI 0.53-1.47, p=0.63) and in the total group (HR=1.02, 95% CI 0.78-1.35, p=0.88), after correcting for effects of intervention. CONCLUSION: Prevalence of MetS is high in Asian Indian IGT subjects, especially in women. However, it did not influence the rate of conversion of IGT to diabetes.