Assessing progression to impaired glucose tolerance and type 2 diabetes mellitus

BACKGROUND: A prospective evaluation of the relationship between insulin secretion and insulin sensitivity, derived from the fasting state, is needed in clinical practice in order to identify the worsening of glucose metabolism. In this study the authors examine whether the product of insulin sensitivity and insulin secretion, assessed from the fasting state, predicts progression from normal glucose tolerance (NGT) to impaired fasting glucose (IFG) and from impaired glucose tolerance (IGT) to type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: A cohort of 300 subjects with NGT and 75 subjects with IGT were followed up over a 5-year period. Insulin sensitivity was calculated using the Belfiore index (B) and insulin secretion by the homeostasis model analysis beta-cell (HOMA-beta cell) index: the product of B-beta is expressed as: (40 x Ins(0) pmol L(-1))/Glu(0) mmol L(-1){[(Glu(0) mmol L(-1)x Ins(0) pmol L(-1)) + 1] - 3.5[(Glu(0) mmol L(-1) x Ins(0) pmol L(-1)) - 1]}, where Glu(0) is fasting glucose and Ins(0) is fasting insulin. RESULTS: From baseline at the end of the follow-up period, the product B-beta decreased 10.7% and 52.2% in progressors to IGT and T2DM, respectively. The product B-beta predicts the progression from NGT to IGT [relative risk (RR) 2.7, CI(95%) 1.2-9.1] and from IGT to T2DM (RR 5.3, CI(95%) 1.3-8.55). The cut-off point for the product B-beta that better predicts progression from NGT to IGT is 0.25 (sensitivity 88%, specificity 92%) and from IGT to T2DM 0.15 (sensitivity 92%, specificity 95%). CONCLUSIONS: Adaptation of insulin secretion to compensate for decreased insulin sensitivity during transition to IGT and T2DM can be successfully assessed with simple measures derived from the fasting state. The product B-beta predicts the development to IGT and T2DM.     

Screening for type 2 diabetes

Definitive studies of the effectiveness of screening for type 2 diabetes are currently not available. RCTs would be the best means to assess effectiveness, but several barriers prevent these studies from being conducted. Prospective observational studies may characterize some of the benefits of screening by creating screened and unscreened groups for comparison. The availability of better data systems and health services research techniques will facilitate such comparisons. Unfortunately, the interpretation of the results of such studies is extremely problematic. Several screening tests have been evaluated. Risk assessment questionnaires have generally performed poorly as stand-alone tests. Screening with biochemical tests performs better. Venous and capillary glucose measurements may perform more favorably than urinary glucose or HbA(1c) measurements, and measuring postprandial glucose levels may have advantages over measuring fasting levels. However, performance of all screening tests is dependent on the cutoff point selected. Unfortunately, there are no well-defined and validated cutoff points to define positive tests. A two-stage screening test strategy may assist with a more efficient use of resources, although such approaches have not been rigorously tested. The optimal interval for screening is unknown. Even though periodic, targeted, and opportunistic screening within the existing health care system seems to offer the greatest yield and likelihood of appropriate follow-up and treatment, much of the reported experience with screening appears to be episodic poorly targeted community screening outside of the existing health care system. Statistical models have helped to answer some of the key questions concerning areas in which there is lack of empirical data. Current models need to be refined with new clinical and epidemiological information, such as the UKPDS results (200). In addition, future models need to include better information on the natural history of the preclinical phase of diabetes. Data from ongoing clinical trials of screening and treatment of impaired glucose tolerance, such as the Diabetes Prevention Program, may eventually offer more direct evidence for early detection and treatment of asymptomatic hyperglycemia (201). It will be important to use comprehensive cardiovascular disease modules that assess the conjoint influence of glucose and cardiovascular risk factor reduction, information on QOL, and refined economic evaluations using common outcome measures (cost per life-year or QALY gained) (11,178,202-204). Such studies should consider all of the costs associated with a comprehensive screening program, including, at a minimum, the direct costs of screening, diagnostic testing, and care for patients with diabetes detected through screening. Finally, combinations of screening tests and different screening intervals should be evaluated within economic studies to allow selection of the optimal approach within the financial and resource limitations of the health care system.     

Associations of adiponectin levels with incident impaired glucose metabolism and type 2 diabetes in older men and women: the hoorn study

OBJECTIVE: Adiponectin is an adipose tissue-derived protein. Low levels are associated with obesity, insulin resistance, and type 2 diabetes. Our objective was to investigate the prospective association between adiponectin levels and the 6.4-year risk of type 2 diabetes and of impaired glucose metabolism (IGM). RESEARCH DESIGN AND METHODS: The Hoorn Study is a cohort study among Caucasians, aged 50-75 years. BMI, waist-to-hip ratio (WHR), fasting glucose, 2-h glucose, triglycerides, HDL cholesterol, LDL cholesterol, alanine aminotransferase, leptin, and adiponectin were measured at baseline. Lifestyle (alcohol intake, smoking, and physical activity) was assessed by questionnaires. After a mean follow-up of 6.4 years, glucose tolerance was assessed by a 75-g oral glucose tolerance test. Analyses were performed in 1,264 subjects (584 men and 680 women) without type 2 diabetes at baseline. For analyses of incident IGM, 239 subjects with IGM at baseline and/or type 2 diabetes at follow-up were excluded. RESULTS: Age- and lifestyle-adjusted odds ratios and 95% CIs comparing highest with lowest adiponectin quartile were 0.52 (0.23-1.18) in men and 0.15 (0.06-0.39) in women for type 2 diabetes and 0.90 (0.51-1.61) and 0.28 (0.16-0.48) for IGM, respectively. The risks were only slightly reduced after adjustment for WHR and leptin as markers of (abdominal) adiposity. Adjustment for baseline fasting and postload glucose levels (potential mediators) substantially diminished these inverse associations with type 2 diabetes (0.79 [0.32-1.91] and 0.62 [0.21-1.81]) and with IGM (1.20 [0.61-2.35] and 0.48 [0.26-0.90]), respectively. CONCLUSIONS: A high adiponectin level was strongly associated with a lower risk of IGM and type 2 diabetes, particularly in women. These results suggest that adiponectin is involved in the pathophysiology linking obesity to type 2 diabetes.     

Screening for type 2 diabetes with random finger‐prick glucose and bedside HbA1c in an Australian emergency department

Objective: To determine if screening for undiagnosed type 2 diabetes mellitus (T2DM) and pre‐diabetes is feasible in an Australian ED; to estimate the prevalence of T2DM and pre‐diabetes in the Australian ED population. Methods: Prospective cross‐sectional prevalence survey in the ED of St Vincent's Hospital, Melbourne, an adult, tertiary referral centre seeing approximately 40 000 patients annually. A convenience sample of adult patients was screened with finger‐prick random blood glucose and glycosylated haemoglobin (HbA1c); those over 6.0 mmol/L and 6.0% were referred for oral glucose tolerance test (OGTT). Diagnoses of T2DM and pre‐diabetes were made according to World Health Organization definitions. Those not attending for OGTT were contacted by phone, and interviewed about their reasons. Results: Seven hundred and twenty‐five patients were recruited; 135 (18.6%; 95% confidence intervals [CI] 15.9–21.6%) had known T2DM, leaving 590 screened, of whom 210 screened positive. Of the 192 referred for OGTT, 147 (77%) did not attend despite several telephone reminders. Of the 45 (23%) completing OGTT, pre‐diabetes was present in eight (17.8%; 95% CI 9.0–31.6%) and T2DM in six (13.3%; 95% CI 5.9–26.6%). Many people interviewed (18/86, 21%) did not attend for OGTT on the advice of their doctors. Conclusions: This inner city tertiary ED has a high prevalence of T2DM, diagnosed and undiagnosed, with as much as half our population possibly affected. Although ED screening might have a high yield, opportunistic screening is not feasible, with difficulties in staff engagement and patient follow up for diagnostic testing. Future studies might consider finger‐prick fasting blood glucose through a patient's general practitioner for diagnosis.     

糖耐量受损和2型糖尿病患者脂联素水平的相关性研究

目的探讨在糖耐量受损及2型糖尿病患者中血脂血糖、胰岛素抵抗和血清脂联素之间的关系。方法 166例分为正常对照组（29例）、糖耐量受损组（41例）和糖尿病组（96例）,分别检测血脂、血糖、血胰岛素水平和血清脂联素,采用HOMA-IR法计算胰岛素抵抗指数。分别对正常组是否进展为糖耐量受损,以及糖耐量受损是否进展为糖尿病进行二分类Logistic回归分析。结果正常对照组、糖耐量受损组和糖尿病组血清脂联素水平分别为（15.8±3.6）、（10.7±2.4）和（6.3±2.4）mg/L,3组间差异有显著统计学意义（P〈0.05）。糖耐量受损组的体质指数、总胆固醇、胰岛素水平和胰岛素抵抗显著高于正常组（P均〈0.05）。Logistic回归分析表明体质指数、高密度脂蛋白胆固醇、空腹胰岛素、胰岛素抵抗指数为正常对照进展为糖耐量受损的危险因素。当糖耐量受损组进展为糖尿病组时,空腹胰岛素是唯一有统计学差异的危险因素。脂联素在两个阶段中都为保护因素。结论在糖耐量受损时胰岛素抵抗水平升高,并已伴随脂联素水平下降。血清脂联素测定,可作为2型糖尿病的辅助诊断、及早干预的指标。     

Abnormal renal and hepatic glucose metabolism in type 2 diabetes mellitus.

Release of glucose by liver and kidney are both increased in diabetic animals. Although the overall release of glucose into the circulation is increased in humans with diabetes, excessive release of glucose by either their liver or kidney has not as yet been demonstrated. The present experiments were therefore undertaken to assess the relative contributions of hepatic and renal glucose release to the excessive glucose release found in type 2 diabetes. Using a combination of isotopic and balance techniques to determine total systemic glucose release and renal glucose release in postabsorptive type 2 diabetic subjects and age-weight-matched nondiabetic volunteers, their hepatic glucose release was then calculated as the difference between total systemic glucose release and renal glucose release. Renal glucose release was increased nearly 300% in diabetic subjects (321+/-36 vs. 125+/-15 micromol/min, P < 0.001). Hepatic glucose release was increased approximately 30% (P = 0.03), but increments in hepatic and renal glucose release were comparable (2.60+/-0.70 vs. 2.21+/-0.32, micromol.kg-1.min-1, respectively, P = 0.26). Renal glucose uptake was markedly increased in diabetic subjects (353+/-48 vs. 103+/-10 micromol/min, P < 0.001), resulting in net renal glucose uptake in the diabetic subjects (92+/-50 micromol/ min) versus a net output in the nondiabetic subjects (21+/-14 micromol/min, P = 0.043). Renal glucose uptake was inversely correlated with renal FFA uptake (r = -0.51, P < 0.01), which was reduced by approximately 60% in diabetic subjects (10. 9+/-2.7 vs. 27.0+/-3.3 micromol/min, P < 0.002). We conclude that in type 2 diabetes, both liver and kidney contribute to glucose overproduction and that renal glucose uptake is markedly increased. The latter may suppress renal FFA uptake via a glucose-fatty acid cycle and explain the accumulation of glycogen commonly found in the diabetic kidney.     

Effects of type 2 diabetes on the regulation of hepatic glucose metabolism.

Glucose production is inappropriately increased in people with type 2 diabetes both before and after food ingestion. Excessive postprandial glucose production occurs in the presence of decreased and delayed insulin secretion and lack of suppression of glucagon release. These abnormalities in hormone secretion, coupled with impaired insulin-induced suppression of glucose production and stimulation of splanchnic glucose uptake, likely account in large part for the excessive amounts of glucose that reach the systemic circulation for disposal by peripheral tissues following food ingestion. In contrast, when adequate basal insulin concentrations are present, neither glucagon-induced stimulation of glucose production nor glucose-induced suppression of glucose production differs in diabetic and nondiabetic subjects matched for gender, age, and degree of obesity. However, when insulin secretion is defective, lack of suppression of glucagon can cause substantial hyperglycemia by enhancing rates of glucose production. Therefore, normalization of hepatic glucose metabolism in people with type 2 diabetes mellitus likely will require normalization of insulin and glucagon secretion as well as hepatic insulin action.     

运用授权理论对糖尿病糖调节受损患者实行行为改变的研究

目的 探讨运用授权理论对新诊断的糖调节受损(IGR)及糖尿病(DM)患者进行授权教育的效果.方法 对54例初次诊断为糖尿病以及IGT、IFG的患者进行为期1年的糖尿病授权教育.分别于授权教育前后,对54例患者检测其血糖、体质量、BMI、收缩压、舒张压、腰围、腰臀比及脂联素.授权教育分为5个步骤:明确问题、表达感情、设立目标、制订计划、评价结果.结果 实行授权教育后,患者的各项指标均有显著改善,P＜0.05.结论 授权教育使患者主动改变生活方式,取得行为改变的目标.     

Regulation of endogenous glucose production by glucose per se is impaired in type 2 diabetes mellitus.

We examined the ability of an equivalent increase in circulating glucose concentrations to inhibit endogenous glucose production (EGP) and to stimulate glucose metabolism in patients with Type 2 diabetes mellitus (DM2). Somatostatin was infused in the presence of basal replacements of glucoregulatory hormones and plasma glucose was maintained either at 90 or 180 mg/dl. Overnight low-dose insulin was used to normalize the plasma glucose levels in DM2 before initiation of the study protocol. In the presence of identical and constant plasma insulin, glucagon, and growth hormone concentrations, a doubling of the plasma glucose levels inhibited EGP by 42% and stimulated peripheral glucose uptake by 69% in nondiabetic subjects. However, the same increment in the plasma glucose concentrations failed to lower EGP, and stimulated glucose uptake by only 49% in patients with DM2. The rate of glucose infusion required to maintain the same hyperglycemic plateau was 58% lower in DM2 than in nondiabetic individuals. Despite diminished rates of total glucose uptake during hyperglycemia, the ability of glucose per se (at basal insulin) to stimulate whole body glycogen synthesis (glucose uptake minus glycolysis) was comparable in DM2 and in nondiabetic subjects. To examine the mechanisms responsible for the lack of inhibition of EGP by hyperglycemia in DM2 we also assessed the rates of total glucose output (TGO), i.e., flux through glucose-6-phosphatase, and the rate of glucose cycling in a subgroup of the study subjects. In the nondiabetic group, hyperglycemia inhibited TGO by 35%, while glucose cycling did not change significantly. In DM2, neither TGO or glucose cycling was affected by hyperglycemia. The lack of increase in glucose cycling in the face of a doubling in circulating glucose concentrations suggested that hyperglycemia at basal insulin inhibits glucose-6-phosphatase activity in vivo. Conversely, the lack of increase in glucose cycling in the presence of hyperglycemia and unchanged TGO suggest that the increase in the plasma glucose concentration failed to enhance the flux through glucokinase in DM2. In summary, both lack of inhibition of EGP and diminished stimulation of glucose uptake contribute to impaired glucose effectiveness in DM2. The abilities of glucose at basal insulin to both increase the flux through glucokinase and to inhibit the flux through glucose-6-phosphatase are impaired in DM2. Conversely, glycogen synthesis is exquisitely sensitive to changes in plasma glucose in patients with DM2.