The relationship of fasting plasma glucose values and other variables to 2-h postload plasma glucose in Japanese subjects.

OBJECTIVE: To investigate the relationship between fasting plasma glucose (FPG) values and other variables (e.g., age, sex, and BMI) to 2-h post-75-g oral glucose load glycemia (PG) in Japanese subjects. RESEARCH DESIGN AND METHODS: Subjects included 13,694 Japanese subjects between 20 and 83 years of age (10,677 men and 3,017 women) who were undergoing a 75-g oral glucose tolerance test (OGTT) during a health screening performed at our hospital. The influences of age for 2-h PG at a fixed fasting plasma glucose (FPG) level of 126 mg/dl were analyzed. Multiple linear regression analysis was performed using a model in which the dependent variable was 2-h PG using the following explanatory variables: FPG, age, sex, BMI, blood pressure, plasma cholesterol, and triglyceride (TG) levels. RESULTS: The 2-h PG at a fixed FPG of 126 mg/dl increased by 0.94 mg/dl per year in patients aged between 30 and 78 years (r = 0.68, P < 0.0001). In multiple regression, five explanatory variables (FPG, age, BMI, plasma TG levels, and systolic blood pressure levels) were all positively associated with 2-h PG. The percentages of patients with 2-h diabetes (isolated postchallenge hyperglycemia [IPH]) versus fasting plus 2-h diabetes by the World Health Organization criteria significantly (P = 0.005) increased as the patients' decades increased, whereas the impact of BMI on the percentages was significant only in young patients (P = 0.001). CONCLUSIONS: Aging was found to be the second best predictor of 2-h PG on multiple regression. Therefore, OGTT should be performed especially in elderly patients because they show IPH more frequently.     

Glucose intolerance is common in Japanese patients with acute coronary syndrome who were not previously diagnosed with diabetes

OBJECTIVE: Postprandial hyperglycemia has emerged as a new glycometabolic condition associated with an excessive risk for coronary artery disease. We therefore attempted to evaluate the frequency of postchallenge hyperglycemia in patients with acute coronary syndrome (ACS) who were not previously diagnosed to have diabetes and did not have a fasting glucose concentration of > or =7 mmol/l or an HbA(1c) level >6.0%. We further correlated the presence of postchallenge hyperglycemia with the extent of coronary atherosclerosis. RESEARCH DESIGN AND METHODS: In all, 134 consecutive ACS patients who met the above inclusion criteria were studied. An oral glucose tolerance test was performed before discharge. RESULTS: The mean age, fasting glucose, and HbA(1c) were 60 years, 5.15 mmol/l, and 5.4%, respectively. Among ACS patients, impaired glucose tolerance (IGT) and diabetes were found in 50 (37%) and 13 patients (10%), respectively. The homeostasis model assessment for insulin resistance did not differ substantially among the normal glucose tolerance (NGT), IGT, and diabetic groups. Insulinogenic index, however, was lower and the number of stenosed vessels higher in diabetic patients compared with NGT patients. CONCLUSIONS: Postchallenge hyperglycemia, caused primarily by impaired initial insulin secretion, is commonly found in Japanese ACS patients who have not been previously diagnosed with diabetes, and this phenomenon is considered to be associated with advanced coronary atherosclerosis. Therefore, the present study strongly supports the notion that oral glucose tolerance test assessment of postchallenge hyperglycemia is essential to identify any previously undiagnosed diabetes cases among Japanese ACS patients.     

Postchallenge hyperglycemia and mortality in a national sample of U.S. adults

OBJECTIVE: Although postchallenge hyperglycemia is a well-established feature of type 2 diabetes, its association with risk of mortality is uncertain. Therefore, the aim of this study was to assess the independent association of fasting and 2-h glucose levels with all-cause and cardiovascular disease (CVD) mortality. RESEARCH DESIGN AND METHODS: We analyzed data from the Second National Health and Nutrition Examination Survey (NHANES II) Mortality Study, a prospective cohort study of U.S. adults examined in the NHANES II, and focused on the 3,092 adults aged 30-74 years who underwent an oral glucose tolerance test at baseline (1976-1980). Deaths were identified from U.S. national mortality files from 1976 to 1992. To account for the complex survey design, we used SUDAAN statistical software for weighted analysis. RESULTS: Compared with their normoglycemic counterparts (fasting glucose [FG] < 7.0 and 2-h glucose < 7.8 mmol/l), adults with fasting and postchallenge hyperglycemia (FG > or =7.0 and 2-h glucose > or =11.1 mmol/l) had a twofold higher risk of death after 16 years of follow-up (age- and sex-adjusted relative hazard [RH] 2.1, 95% CI 1.4-3.2). However, adults with isolated postchallenge hyperglycemia (FG < 7.0 and 2-h glucose > or =11.1 mmol/l) were also at higher risk of death (1.6, 1.0-2.6). In proportional hazards analysis, FG (fully adjusted RH 1.10 per 1 SD; 95% CI 1.01, 1.22) and 2-h glucose (1.14, 1.00-1.29) showed nearly identical predictive value for mortality. Similar trends were observed for CVD mortality. CONCLUSIONS: These results suggest that postchallenge hyperglycemia is associated with increased risk of all-cause and CVD mortality independently of other CVD risk factors.     

Risk of diabetes in the new diagnostic category of impaired fasting glucose: a prospective analysis.

OBJECTIVE: To prospectively evaluate progression to diabetes in individuals with impaired glucose regulation as defined according to fasting glucose alone or an oral glucose tolerance test (OGTT) (i.e., both fasting and postload glucose) to compare the ability of these two screening methods to identify people at high risk of developing diabetes. RESEARCH DESIGN AND METHODS: A working population of 1,245 nondiabetic telephone company employees aged 40-59 years was studied by OGTT in 1980. Participants were classified according to baseline fasting glucose only (as encouraged by the American Diabetes Association [ADA]) or OGTT (as recommended by the 1998 World Health Organization [WHO] consultation). Progression to diabetes was evaluated 11.5 years later according to the 1997 ADA criteria of a fasting plasma glucose level > or =7.0 mmol/l. RESULTS: With the use of the OGTT, baseline prevalence of impaired glucose regulation was substantially higher than that with fasting glucose alone (7.2 vs. 3.2%); the two groups only overlap for 40.9% of the cases because a fairly large number of people with postload hyperglycemia (59.1%) have normal fasting glucose. Progression to diabetes in participants with normal fasting glucose and postload hyperglycemia is significantly more frequent than that of people with normoglycemia (32.5 vs. 7.2%; P < 0.001) and not significantly different from that of people with both fasting and postload hyperglycemia (i.e., 44.0%). However, the former are not identified as being at unusually high risk of diabetes unless an OGTT is performed. When the use of fasting glucose alone or OGTT was validated as a marker of progression to diabetes, sensitivity was substantially higher for the OGTT (33.3 vs. 9.0%) without major differences in specificity (92.6 vs. 97.0%). CONCLUSIONS: These data (the only data so far available in Caucasians) support the viewpoint that for the identification of people at high risk of diabetes, the use of the OGTT should be maintained.     

Increased prevalence of impaired glucose tolerance in patients with painful sensory neuropathy

OBJECTIVE: To characterize a cohort of patients with neuropathy and impaired glucose tolerance (IGT) but no other identifiable cause of neuropathy. Of patients with diabetes, 10% have peripheral neuropathy at the time of their diagnosis, suggesting that axonal injury may occur early in the course of glucose intolerance. The American Diabetes Association (ADA) revised diagnostic criteria to recognize IGT (a serum glucose between 140 and 200 mg/dl in a 2-h oral glucose tolerance test [OGTT]) as a risk factor for cardiovascular disease independent of development of diabetes. RESEARCH DESIGN AND METHODS: Using revised ADA criteria for diabetes and IGT, we prospectively evaluated 107 sequential patients with idiopathic neuropathy. RESULTS: A total of 13 of the 107 patients had diabetes, whereas 36 (34%) had IGT, nearly three times the prevalence in age-matched control subjects (P < 0.01). OGTT was often elevated, whereas both fasting plasma glucose and HbA(1c) were normal. Comparing patients with diabetes, IGT, or normal OGTT, age and BMI were similar. However, painful sensory symptoms were more common in patients with IGT and diabetes, and family history of neuropathy was significantly more common in normoglycemic patients. Electrodiagnostic findings of axonal injury were less severe in patients with IGT and were more likely to be confined to sensory fibers than in patients with diabetes. CONCLUSIONS: Our results suggest that IGT may cause or contribute to small-fiber neuropathy, which is similar in phenotype to the painful sensory neuropathy commonly encountered in diabetes. Two-hour OGTT is more sensitive than other measures of glucose handling in screening these patients.     

HbA1c measurement improves the detection of type 2 diabetes in high-risk individuals with nondiagnostic levels of fasting plasma glucose: the Early Diabetes Intervention Program (EDIP)

OBJECTIVE: Whereas new diagnostic criteria based on a fasting plasma glucose (FPG) of > 126 mg/dl (7.8 mmol/l) have improved the detection of diabetes, multiple reports indicate that many people with diabetes diagnosed by 2-h oral glucose tolerance test (OGTT) glucose measurements > or = 11.1 mmol/l (200 mg/dl) would remain undiagnosed based on this FPG criteria. Thus, improved methods to detect diabetes are particularly needed for high-risk individuals. We evaluated whether the combination of FPG and HbA1c measurements enhanced detection of diabetes in those individuals at risk for diabetes with nondiagnostic or minimally elevated FPG. RESEARCH DESIGN AND METHODS: We analyzed FPG, OGTT, and HbA1c data from 244 subjects screened for participation in the Early Diabetes Intervention Program (EDIP). RESULTS: Of 244 high-risk subjects studied by FPG measurements and OGTT, 24% of the individuals with FPG levels of 5.5-6.0 mmol/l (100-109 mg/dl) had OGTT-diagnosed diabetes, and nearly 50% of the individuals with FPG levels of 6.1-6.9 mmol/l (110-125 mg/dl) had OGTT-diagnosed diabetes. In the subjects with OGTT-diagnosed diabetes and FPG levels between 5.5 and 8.0 mmol/l, detection of an elevated HbA1c (>6.1% or mean + 2 SDs) led to a substantial improvement in diagnostic sensitivity over the FPG threshold of 7.0 mmol/l (61 vs. 45%, respectively, P = 0.002). Concordant FPG levels > or = 7.0 mmol/l (currently recommended for diagnosis) occurred in only 19% of our cohort with type 2 diabetes. CONCLUSIONS: Diagnostic criteria based on FPG criteria are relatively insensitive in the detection of early type 2 diabetes in at-risk subjects. HbA1c measurement improves the sensitivity of screening in high-risk individuals.     

From policemen to policies: what is the future for 2-h glucose? The Kelly West Lecture, 2000.

OBJECTIVE: To describe the characteristics and vital prognosis of men with diabetes diagnosed by one fasting plasma glucose (FPG) concentration > or =7.0 mmol/l, with diabetes diagnosed by one isolated postchallenge hyperglycemia (IPH) (FPG <7.0 mmol/l and a 2-h plasma glucose concentration > or =11.1 mmol/l), or with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: This study involved a cohort of 6,881 Caucasian nondiabetic men from the Paris Prospective Study, aged 44-55 years, who were followed for cause of death for 20 years. RESULTS: Diabetes was diagnosed in 4.3% of the men (1.0% diabetes diagnosed by IPH), and IGT was diagnosed in 9% of the men. At baseline, the men with diabetes diagnosed by IPH had a lower cardiovascular risk profile than those with diabetes diagnosed by FPG, as did the men with IGT and a normal fasting glucose level (<6.1 mmol/l, IGT and normal fasting glucose), compared with men with impaired fasting glucose (6.1-6.9 mmol/l, IGT and impaired fasting glucose [IFG]). At 20 years of follow-up, all-cause and cancer death rates were higher in men with diabetes diagnosed by IPH than in men with diabetes diagnosed by FPG (55 vs. 44%, P < 0.1 and 31 vs. 17%, P < 0.01, respectively) but were not significantly different for coronary causes (6 vs. 11%). Men with IGT and normal fasting glucose also had significantly higher cancer death rates than men with IGT and IFG. CONCLUSIONS: The most likely explanation for the high cancer and low coronary death rates is that men with diabetes diagnosed by IPH consumed alcohol; the men in this study drank 49 g of pure alcohol on average per day, equivalent to 0.6 l of wine. If these results are confirmed by other prospective studies, screening subjects for isolated postchallenge hyperglycemia may not be worthwhile.     

Reproducibility of the diagnosis of diabetes over a 30-month follow-up: the Paris Prospective Study.

OBJECTIVE: To describe the change in diabetic status over 30 months. RESEARCH DESIGN AND METHODS: Cohort study of 5,400 Caucasian men from the Paris Prospective Study, aged 44-55 years, who were not known as having diabetes at baseline. Oral glucose tolerance tests were performed at baseline and after 30 months. RESULTS: At baseline, diabetes was diagnosed in 2.9% of the men by fasting plasma glucose (FPG) > or =7.0 mmol/l and in 0.9% by isolated postchallenge hyperglycemia (IPH) (FPG <7.0 mmol/l and 2-h plasma glucose concentration > or =11.1 mmol/l), i.e., one in four of all men with newly diagnosed diabetes. Thirty months later, 42% of the men with diabetes diagnosed by FPG reverted to nondiabetic status, compared with 72% of those with diabetes diagnosed by IPH (P < 0.0001). For the men with diabetes diagnosed by FPG at baseline, diabetes had been diagnosed by a physician at 30 months in 11.5%, in contrast to only 3.9% of those with diabetes diagnosed by IPH (P < 0.05). For the 51 men with diabetes diagnosed by IPH at baseline, those who reverted to nondiabetic status had a lower frequency of family history of diabetes (P < 0.1), a higher mean corpuscular volume (P < 0.08), and a significantly higher total cholesterol concentration (P < 0.006) at baseline; in contrast, for the 156 men with diabetes diagnosed by FPG at baseline, the men who reverted to nondiabetic status and those who remained diabetic had similar characteristics. CONCLUSIONS: In this epidemiological study, diabetes diagnosed by one FPG concentration was more stable than diabetes diagnosed by one IPH; in clinical practice, the diagnosis of diabetes requires confirmation of the hyperglycemia.     

The prevalence of diabetes in the kingdom of Tonga

OBJECTIVE: To determine the prevalence of diabetes, impaired glucose metabolism, and related risk factors in Tonga. RESEARCH DESIGN AND METHODS: A randomly selected representative national sample of 1,024 people aged >15 years was surveyed. Each participant had fasting blood glucose and HbA(1c) measured. Subjects with a fasting blood glucose >5.0 mmol/l (90 mg/dl) and <11.1 mmol/l (200 mg/dl) or a fasting blood glucose < or =5.0 mmol/l and an HbA(1c) >6.0% and every fifth subject with a fasting blood glucose < or =5.0 mmol/l and a normal HbA(1c) had a 75-g oral glucose tolerance test (OGTT). A total of 472 individuals had an OGTT based on these criteria. Subjects with a fasting blood glucose > or =11.1 mmol/l and an elevated HbA(1c) were diagnosed as having diabetes. RESULTS: The mean age was 41.3 years, and the mean BMI was 32.3 kg/m(2). The age-standardized prevalence of diabetes was 15.1% (CI 12.5-17.6), 12.2% (8.7-15.8) in men and 17.6% (14.0-21.1) in women (NS), of which only 2.1% was previously diagnosed. A total of 75% of people with newly diagnosed diabetes had a fasting plasma glucose > or =7.0 mmol/l (126 mg/dl). The prevalence of impaired glucose tolerance was 9.4% (7.3-11.5) and of impaired fasting glycemia 1.6% (0.7-2.6). Undiagnosed diabetes was significantly associated with increasing age, obesity, hypertension, and a family history of diabetes. CONCLUSIONS: The current prevalence of diabetes in Tonga is 15.1%, of which 80% is undiagnosed. A similar survey in 1973 reported a 7.5% diabetes prevalence, indicating a doubling of diabetes over the past 25 years. In addition, lesser degrees of glucose intolerance are common, and much of the community is overweight     

Prevalence of undiagnosed diabetes in three American Indian populations. A comparison of the 1997 American Diabetes Association diagnostic criteria and the 1985 World Health Organization diagnostic criteria: the Strong Heart Study

OBJECTIVE: In 1997, the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus of the American Diabetes Association (ADA) recommended three new sets of criteria for the diagnosis of diabetes that were different from those established by the World Health Organization (WHO) in 1985. One of these three methods was based on a fasting plasma glucose value only. This article compares ADA criteria with WHO criteria by applying them to three subgroups of American Indians in the Strong Heart Study who had no known diabetes. RESEARCH DESIGN AND METHODS: The Strong Heart Study is a prospective epidemiological study of vascular disease in three American Indian populations aged 45-74 years. During the baseline examination from 1988 to 1991, participants without diagnosed diabetes underwent a fasting glucose test and a 2-h oral glucose tolerance test. These values were used to compare the ADA and WHO diagnostic criteria. RESULTS: By using fasting and 2-h glucose values, prevalence rates of undiagnosed diabetes were 15.9% according to WHO criteria and 14.4% according to ADA criteria. The overall agreement rate was 65%, and the weighted kappa statistic was 0.474, which indicates moderate agreement. The age-specific analysis showed that, among participants between 45 and 54 years of age, the prevalence rates of undiagnosed diabetes were 13.4% according to WHO criteria and 12.7% according to ADA criteria. Among those aged 55-74 years, the rates were 18.7% according to WHO criteria and 16.3% according to ADA criteria. Thus, the difference in the prevalence rates when using WHO and ADA criteria, although generally small in this population, was three times higher in the older group (2.4%) than the difference in the younger group (0.7%). CONCLUSIONS: The Strong Heart Study found that prevalence rates of undiagnosed diabetes determined by ADA criteria and WHO criteria were similar in its American Indian population. The data suggest that the difference between the two criteria may increase as age increases. Longitudinal data will be needed to evaluate further the utility of the two criteria.     

Screening for type 2 diabetes and impaired glucose metabolism: the Australian experience

OBJECTIVE: To assess the Australian protocol for identifying undiagnosed type 2 diabetes and impaired glucose metabolism. RESEARCH DESIGN AND METHODS: The Australian screening protocol recommends a stepped approach to detecting undiagnosed type 2 diabetes based on assessment of risk status, measurement of fasting plasma glucose (FPG) in individuals at risk, and further testing according to FPG. The performance of and variations to this protocol were assessed in a population-based sample of 10,508 Australians. RESULTS: The protocol had a sensitivity of 79.9%, specificity of 79.9%, and a positive predictive value (PPV) of 13.7% for detecting undiagnosed type 2 diabetes and sensitivity of 51.9% and specificity of 86.7% for detecting impaired glucose tolerance (IGT) or impaired fasting glucose (IFG). To achieve these diagnostic rates, 20.7% of the Australian adult population would require an oral glucose tolerance test (OGTT). Increasing the FPG cut point to 6.1 mmol/l (110 mg/dl) or using HbA(1c) instead of FPG to determine the need for an OGTT in people with risk factors reduced sensitivity, increased specificity and PPV, and reduced the proportion requiring an OGTT. However, each of these protocol variations substantially reduced the detection of IGT or IFG. CONCLUSIONS: The Australian screening protocol identified one new case of diabetes for every 32 people screened, with 4 of 10 people screened requiring FPG measurement and 1 in 5 requiring an OGTT. In addition, 1 in 11 people screened had IGT or IFG. Including HbA(1c) measurement substantially reduced both the number requiring an OGTT and the detection of IGT or IFG.     

Postchallenge plasma glucose and glycemic spikes are more strongly associated with atherosclerosis than fasting glucose or HbA1c level

OBJECTIVE: To observe the relationship of fasting plasma glucose (FPG), postchallenge plasma glucose (PG) (30, 60, 90, and 120 min during an oral glucose tolerance test [OGTT], as well as maximal PG during an OGTT, postchallenge glucose spikes [PGS], and glucose under the OGTT curve), and HbA1c to intima-media thickness (IMT) as a marker of atherosclerosis. RESEARCH DESIGN AND METHODS: OGTT, ultrasound measurement of carotid IMT, and various atherosclerosis risk factors, such as family history of diabetes, obesity, and/or hyperlipoproteinemia, but without known diabetes, were analyzed in 582 individuals aged 40-70 years and at risk for type 2 diabetes. RESULTS: In univariate analysis, all examined glycemic parameters were significantly correlated to IMT. The 2-h postchallenge plasma glucose showed the strongest odds ratio (OR) of 1.88 (1.34-2.63) in relation to abnormal IMT. All PG variables, except for 30-min glucose in OGTT, showed a significant OR, whereas the OR for HbA1c and FPG was not significant. In logistic regression analysis, 2-h PG was identified as the strongest determinant of IMT from all glycemic parameters. The 2-h PG and PGS, but not FPG, were associated with a significant rise of IMT in tertiles of HbA1c. Glycemic parameters were strongly related to each other and to many atherosclerosis risk factors. In multivariate analysis including a variety of atherosclerosis risk factors, 2-h PG was a significant independent determinant of IMT. CONCLUSIONS: PG and PGS are more strongly associated with carotid IMT than FPG and HbA1c level and modify substantially the risk for atherosclerosis, estimated by HbA1c alone, in a cohort at risk for diabetes and in the early diabetes stage.     

Utility of HbA(1c) levels for diabetes case finding in hospitalized patients with hyperglycemia

OBJECTIVE: We evaluated the role of a single measurement of HbA(1c) in a diabetes case finding in hospitalized patients with random hyperglycemia at admission. RESEARCH DESIGN AND METHODS: From 20 March to 31 July 2000, 508 patients admitted through the emergency department of one hospital were tested for random hyperglycemia (plasma glucose [PG] >125 mg/dl). Consenting patients with hyperglycemia (without preexisting diabetes or on corticosteroids) underwent testing for HbA(1c) levels, two fasting PG levels, and an outpatient oral glucose tolerance test (OGTT) if necessary. RESULTS: Of the patients, 50 (9.8%) met the inclusion criteria. Of these, 70% (n = 35) completed the study, and 60% (n = 21) were diagnosed with diabetes. Patients with diabetes had higher HbA(1c) levels than subjects without diabetes (6.8 +/- 0.4 vs. 5.3 +/- 0.1%, P = 0.002). An HbA(1c) level >6.0% was 100% specific (14/14) and 57% sensitive (12/21) for the diagnosis of diabetes. When a lower cutoff value of HbA(1c) at 5.2% was used, specificity was 50% (10/21) and sensitivity was 100% (7/14). CONCLUSIONS: In acutely ill patients with random hyperglycemia at hospital admission, an HbA(1c) >6.0% reliably diagnoses diabetes, and an HbA(1c) level <5.2% reliably excludes it (paralleling the operating characteristics of the standard fasting glucose measurements); however, the rapidity of the HbA(1c) level can be useful for diabetes case finding and treatment initiation early in the hospital course.     

High incidence of glucose intolerance in Asian-Indian subjects with acute coronary syndrome

OBJECTIVE: The risk of diabetes and coronary heart disease is high in Asian Indians. In this study, we aim to assess 1) the prevalence of hyperglycemia in incident acute coronary syndrome (ACS), 2) the effect of glycemia on the outcome, and 3) the association of plasma levels of insulin and proinsulin with ACS. RESEARCH DESIGN AND METHODS: A total of 146 nondiabetic subjects (121 men, 25 women) with ACS admitted to two hospitals in 1 year were enrolled. Random blood glucose at admission and a standard oral glucose tolerance test within 3 days were done. Glucose tolerance was categorized as normal glucose tolerance, impaired glucose tolerance (IGT) or impaired fasting glucose, and diabetes. Diabetes was arbitrarily classified further as undiagnosed (HbA1c [A1C] >6.0%) or possibly stress diabetes (A1C <6.0%). Subjects not on antidiabetic treatment were reassessed with a glucose tolerance test between 1 and 2 months. Fasting plasma specific insulin, proinsulin, their molar ratios, and insulin resistance (homeostasis model assessment) were estimated at baseline. RESULTS: Mean age of the cohort was 55 +/- 10.6 (SD) years. At baseline, 24 (16.4%) had normal glucose tolerance, 67 (45.9%) had IGT or impaired fasting glucose, and 55 (37%) had diabetes (35 [24%] were undiagnosed and 20 [13.7%] had stress diabetes). At follow-up, 53 of 92 responders (57.6%) continued to have IGT or diabetes. Mean baseline plasma insulin, proinsulin and its ratios, and insulin resistance were higher than normal in all subgroups. CONCLUSIONS: Nondiabetic Asian Indians showed a high prevalence of hyperglycemia following ACS. ACS was associated with insulin resistance and increased levels of specific insulin, proinsulin, and high proinsulin-to-insulin ratios.     

Screening, diagnosis and management of diabetes mellitus and diabetic complications

Diabetes mellitus comprises a group of metabolic disturbances that are characterized by hyperglycemia. In 1997 the American Diabetes Association (ADA) proposed new criteria for the diagnosis and classification of diabetes mellitus, which was also adopted by WHO. Although the criteria is the same, the ADA puts emphasis on the use of the fasting plasma glucose (FPG) for screening and diagnosis, whereas WHO maintains the use of the OGTT and recommends the FPG only if an OGTT can not be performed. Different pathogenetic processes are involved in the development of diabetes ranging from autoimmune destruction of beta-cells resulting in an absolute insulin deficiency to insulin with a defect on insulin secretion. The new classification is based on the etiology of the disease. Diabetes is classified into one of four categories: Type-1, type-2 Diabetes mellitus, specific forms of diabetes, and gestational diabetes. For screening and diagnosis FPG or the two hour value after the OGTT can be used. Glycosylated hemoglobin is not suitable for screening and diagnosis of diabetes despite some contradictory statements. For many decades clear evidence was missing that chronic hyperglycemia caused diabetic late complications; complications including dysfunction or failure of several organ systems, in particular eyes, kidneys, nerves, and the cardiovascular system. The results of two large prospective trials--the Diabetes Control and Complications Trial (DCCT; 1993) and the United Kingdom Prospective Study (UKPDS; 1998)--that were recently published provided the final proof that normoglycemia prevents or delays the progression of these late complications. Due to the insidious nature of these complications they are often not diagnosed and have to be looked for in each patients with diabetes and have to be controlled regularly. Based on the results of the UKPDS and other studies, evidence based therapeutic goals could be defined. Multifactorial interventions with increased physical activity, cessation of smoking, aspirin treatment, lowering of HbA1c, blood pressure, and lipids in patients with type 2 diabetes have been proven to drastically reduce the risk of developing diabetic nephropathy or cardiovascular complications drastically. We recommend the following treatment strategy for patients with type 2 diabetes in clinical practice: 1) Treatment should be individualized. 2) Treatment should be started step by step to document efficacy of treatment and compliance of patients. 3) Plasma glucose and blood pressure should be normalized in all patients with type 2 diabetes (up to an age of 70 years), since there are no threshold values for HbA1c and blood pressure. 4) Therapeutic goals should be checked every three to six months. 5) In the case that therapeutic goals can not be met, treatment should be intensified. Often a combination therapy with many different drugs is required. 6) A specialist for diabetes should be consulted, if the therapeutic goals can not be met over a period of six months.     

Projected impact of implementing the results of the diabetes prevention program in the U.S. population

OBJECTIVE: To determine the feasibility of using either fasting plasma glucose or HbA(1c) to identify individuals in the U.S. population who meet the Diabetes Prevention Program (DPP) criteria for intervention, defined as BMI >/=24 kg/m(2), fasting plasma glucose level 96-125 mg/dl, and 2-h glucose level 140-199 mg/dl in an oral glucose tolerance test (OGTT). RESEARCH DESIGN AND METHODS: Analysis of a representative sample of U.S. adults aged 40-74 years with no medical history of diabetes for whom data on height, weight, fasting plasma glucose, HbA(1c), and 2-h plasma glucose during an OGTT were obtained. Sensitivity, specificity, positive predictive value (PPV), and receiver operator characteristic (ROC) curves for fasting glucose and HbA(1c) were determined. RESULTS: Using BMI <24 kg/m(2) as an initial criterion eliminated 27.2% of U.S. adults from further testing. Of the remaining group, 41.1% did not have to be considered for an OGTT because their fasting glucose level was below or above 96-125 mg/dl. Overall, 10.6% of adults aged 40-74 years without medical history of diabetes met the DPP eligibility criteria for intervention. Among individuals with BMI >/=24 kg/m(2) and fasting glucose level 96-125 mg/dl, applying a fasting plasma glucose cutoff of >/=105 mg/dl excluded 62.5% of this group and resulted in 56.0% of those with 2-h glucose level 140-199 mg/dl in this group being identified, with a specificity of 72.0% and a PPV of 17.1%. Similar values were obtained for an HbA(1c) cutoff value of >/=5.5%. CONCLUSIONS: Using data on BMI and setting cutoff values for fasting glucose and HbA(1c) would greatly reduce the number of individuals who would need to undergo an OGTT while achieving adequate sensitivity, specificity, and PPV.     

Factors responsible for development from normal glucose tolerance to isolated postchallenge hyperglycemia

OBJECTIVE: Isolated postchallenge hyperglycemia (IPH), defined as fasting plasma glucose (FPG) level <7.0 mmol/l and 2-h plasma glucose (PG) level >/=11.1 mmol/l, is a subtype of early-stage diabetes. This study evaluates the metabolic profiles of insulin secretion and insulin sensitivity in IPH to clarify the factors responsible for development of this form of type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted cross-sectional analysis of 231 Japanese men aged 20-70 years. The subjects were classified into the following three groups, based on the results of a 75-g oral glucose tolerance test (OGTT): 1) normal glucose tolerance (NGT), defined as FPG level <6.1 mmol/l and 2-h PG level <7.8 mmol/l (n = 89); 2) impaired glucose tolerance (IGT), defined as FPG level <7.0 mmol/l and 2-h PG level of 7.8-11.1 mmol/l (n = 94); and 3) IPH (n = 48). We compared the three groups for insulin secretion (insulinogenic index) and insulin sensitivity (index of insulin resistance using homeostasis model assessment [HOMA-IR]). RESULTS: The insulinogenic index in IPH was the lowest of the three groups (P < 0.001 versus NGT). The HOMA-IR in the IGT and IPH groups were significantly higher than in the NGT group (P < 0.001), but both were similar. By linear regression analysis, the insulinogenic index rather than fasting insulin or HOMA-IR was the more significant factor in the 2-h PG level in IGT and IPH. CONCLUSIONS: Subjects with IPH exhibited distinctly impaired early-phase insulin secretion and only mild insulin resistance, indicating that reduced insulin secretion is the primary determinant of deterioration from NGT to IGT and IPH in development of type 2 diabetes in these subjects.     

Gestational diabetes mellitus diagnosed with a 2-h 75-g oral glucose tolerance test and adverse pregnancy outcomes.

OBJECTIVE: To evaluate American Diabetes Association (ADA) and World Health Organization (WHO) diagnostic criteria for gestational diabetes mellitus (GDM) against pregnancy outcomes. RESEARCH DESIGN AND METHODS: This cohort study consecutively enrolled Brazilian adult women attending general prenatal clinics. All women were requested to undertake a standardized 2-h 75-g oral glucose tolerance test (OGTT) between their estimated 24th and 28th gestational weeks and were then followed to delivery. New ADA criteria for GDM require two plasma glucose values > or = 5.3 mmol/l (fasting), > or = 10 mmol/l (1 h), and > or = 8.6 mmol/l (2 h). WHO criteria require a plasma glucose > or = 7.0 mmol/l (fasting) or > or = 7.8 mmol/l (2 h). Individuals with hyperglycemia indicative of diabetes outside of pregnancy were excluded. RESULTS: Among the 4,977 women studied, 2.4% (95% CI 2.0-2.9) presented with GDM by ADA criteria and 7.2% (6.5-7.9) by WHO criteria. After adjustment for the effects of age, obesity, and other risk factors, GDM by ADA criteria predicted an increased risk of macrosomia (RR 1.29, 95% CI 0.73-2.18), preeclampsia (2.28, 1.22-4.16), and perinatal death (3.10, 1.42-6.47). Similarly, GDM by WHO criteria predicted increased risk for macrosomia (1.45, 1.06-1.95), preeclampsia (1.94, 1.22-3.03), and perinatal death (1.59, 0.86-2.90). Of women positive by WHO criteria, 260 (73%) were negative by ADA criteria. Conversely, 22 (18%) women positive by ADA criteria were negative by WHO criteria. CONCLUSIONS: GDM based on a 2-h 75-g OGTT defined by either WHO or ADA criteria predicts adverse pregnancy outcomes.     

Age does not influence levels of HbA1c in normal subject.

To resolve whether haemoglobin A1c(HbA1c) levels in normal subjects increase with age, we measured HbA1c in 399 patients undergoing routine oral glucose tolerance test (OGTT). The OGTT results categorized the patients into 127 normal, 94 impaired glucose tolerance (IGT) and 178 diabetic. None of these groups showed a significant correlation between HbA1c and age and we cannot, therefore, see a need for age-specific reference ranges for HbA1c. Some of the confusion in the literature may have arisen from less rigorous categorization of subjects than we used, resulting in the inclusion of some individuals with IGT or diabetes in the 'normal' groups of other studies. The prevalence of such abnormality would be expected to be greater amongst older subjects, falsely suggesting a correlation between HbA1c and age, and we were able to demonstrate this with our own data when insufficiently rigorous criteria were applied for the selection of normal subjects.     

Efficient cutoff points for three screening tests for detecting undiagnosed diabetes and pre-diabetes: an economic analysis

OBJECTIVE: Opportunistic screening for undiagnosed type 2 diabetes and pre-diabetes (either impaired glucose tolerance or impaired fasting glucose) is recommended by the American Diabetes Association. The aim of this study was to determine efficient cutoff points for three screening tests for detecting undiagnosed diabetes alone or both undiagnosed diabetes and pre-diabetes. RESEARCH DESIGN AND METHODS: We estimated the number of individuals with undiagnosed diabetes alone or with both undiagnosed diabetes and pre-diabetes that could be detected by using different cutoff points for each screening test as the product of the prevalence of each condition, the sensitivity of the tests at each cutoff point for identifying each condition, and the number of individuals who would be eligible for screening in the U.S. We estimated the total cost of opportunistic screening by multiplying the cost for screening one person by the number of individuals screened. RESULTS: The most efficient cutoff points for both detecting pre-diabetes and undiagnosed diabetes (100 mg/dl for the fasting plasma glucose test, 5.0% for the HbA(1c) test, and 100 mg/dl for the random capillary blood glucose test) were less than those for detecting undiagnosed diabetes alone (110 mg/dl for the fasting plasma glucose test, 5.7% for the HbA(1c) test, and 120 mg/dl for the random capillary blood glucose test). CONCLUSIONS: A lower cutoff value should be used when screening for pre-diabetes and undiagnosed diabetes together than when screening for undiagnosed diabetes alone.