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Expert clinicians counter some of the recommendations regarding hemoglobin A1c targets for type 2 diabetes that were proposed in a recent American College of Physicians guideline.

In the United States, 9.4% of all adults-and 25% of those older than 65 years-have diabetes. Diabetes is the leading cause of blindness and end-stage renal disease and contributes to both microvascular and macrovascular complications. The management of patients with type 2 diabetes (T2D) is a common and important activity in primary care internal medicine practice. Measurement of hemoglobin A1c (HbA1c) provides an estimate of mean blood sugar levels and glycemic control. The optimal HbA1c target level among various persons with T2D is a subject of controversy. Guidelines regarding HbA1c targets have yielded differing recommendations. In 2018, the American College of Physicians (ACP) published a guideline on HbA1c targets for nonpregnant adults with T2D. In addition to a recommendation to individualize HbA1c target levels, the ACP proposed a level between 7% and 8% for most patients. The ACP also advised deintensification of therapy for patients who have an HbA1c level lower than 6.5% and avoidance of HbA1c-targeted treatment for patients with a life expectancy of less than 10 years. This guidance contrasts with a recommendation from the American Diabetes Association to aim for HbA1c levels less than 7% for many nonpregnant adults and to consider a target of 6.5% if it can be achieved safely. Here, 2 experts, a diabetologist and a general internist, discuss how to apply the divergent guideline recommendations to a patient with long-standing T2D and a current HbA1c level of 7.8%.

In this issue, Buse and colleagues report that twice-daily exenatide was superior to placebo for reducing hemoglobin A1c levels in people with type 2 diabetes who are receiving insulin glargine. Th...

Despite the growing number of options for treating type 2 diabetes, clinicians wanting to prevent the disease in high-risk patients have few good choices. Two large trials in 2002 showed that metfo...

Objective : To examine the putative pathogenetic mechanisms of the long-term, specific complications of diabetes mellitus. Data Sources : Literature review relevant to long-term diabetic complications and their pathogenesis. Study Selection : Studies of animal models of diabetes, epidemiologic investigations of diabetes and its long-term complications, and interventional studies examining intensive treatment of diabetes and its effect on the development and progression of complications. Data Synthesis : Diabetic retinopathy, nephropathy, and neuropathy occur in all clinical forms of diabetes mellitus, regardless of the cause of the diabetes. Hyperglycemia appears to be the major variable shared among these different clinical forms ; and epidemiologic data, studies in animal models of diabetes, and the results of recent interventional studies such as the Diabetes Control and Complications Trial, all support an important and perhaps dominant role of hyperglycemia in the pathogenesis of complications. However, the diverse complications may not share the same pathogenesis. Different pathogenetic mechanisms may operate in different types of diabetic complications or at different stages of specific complications, or both. Conclusions : The level of chronic glycemia is the best established concomitant factor associated with diabetic complications. The mechanism by which hyperglycemia might cause complications remains unknown, and evidence for a uniform pathogenetic mechanism is far from established.

Recent observational studies—including Greenfield and colleagues' 5-year cohort study in this issue—aim to define appropriate treatment goals for patients with type 2 diabetes and whether achieving...

Hoerger and colleagues have used decision modeling to advance our understanding of the benefit of screening for diabetes in people with and without hypertension. However, without optimized manageme...

This paper discusses tests of glycemia for the diagnosis of type 2 diabetes mellitus, with particular reference to the 1997 diagnostic criteria of the American Diabetes Association. The potential benefits of the lower diagnostic threshold for fasting plasma glucose are not well defined. However, the change in the diagnostic cut-off for diabetes mellitus affects as many as 1.9 million persons in the United States; therefore, the medical and social costs of the lower threshold may be considerable. Type 2 diabetes mellitus is defined by a threshold imposed on the continuous distribution of glycemic levels, typically with respect to risk for microvascular complications. However, the burden of type 2 diabetes relates more to macrovascular than microvascular complications. Because no clear threshold exists for macrovascular complications, a formal balancing of direct and indirect costs with both microvascular and macrovascular complications may be appropriate to establish glycemic thresholds. Because fasting plasma glucose, hemoglobin A1c, and the oral glucose tolerance test all predict diabetic complications yet test reliability is better for fasting plasma glucose and hemoglobin A1c than for the oral glucose tolerance test, we suggest an alternative diagnostic approach: If random plasma glucose is elevated (> or =11.1 mmol/L [200 mg/dL]) and the hemoglobin A1c level is more than 2 SDs above the laboratory mean, then diabetes mellitus should be diagnosed, and management should be based on the hemoglobin A1c level. If the result of only one of these tests is positive, then fasting plasma glucose should be tested to evaluate the patient for impaired fasting glucose and diabetes mellitus. The glycemic threshold for type 2 diabetes should be established by cost-effectiveness analysis. The clinical diagnosis of diabetes mellitus could be streamlined by incorporation of hemoglobin A1c into established criteria.

In this issue, Cefalu and colleagues report findings from a 3-month study of inhaled insulin in patients with type 2 diabetes. Can we draw any conclusions about this method of delivering insulin, c...

The study by Yki-Jarvinen and colleagues in this issue adds to the accumulating data supporting the idea that intensive therapy goals can be achieved in patients with type 2 diabetes, with relative...

Categorical definitions for glucose intolerance imply that risk thresholds exist, but metabolic risk for type 2 diabetes mellitus or cardiovascular disease may increase continuously as glucose intolerance increases.To examine the distributions of the following metabolic risk factors across the spectrum of glucose tolerance: overall and central obesity, hypertension, low levels of high-density lipoprotein cholesterol, and increased triglyceride and insulin levels.Cross-sectional analysis.The community-based Framingham Offspring Study.2583 adults without previously diagnosed diabetes.Clinical data; fasting glucose, insulin, and lipid levels; and glucose and insulin levels taken 2 hours after oral challenge were collected from 1991 to 1993. Glucose tolerance was determined by 1980 World Health Organization criteria. Patients with normal glucose tolerance were categorized into quintiles of fasting glucose. The distributions of each metabolic risk factor and the metabolic sum of the six risk factors were assessed across seven categories from the lowest quintile of normal fasting glucose level through impaired glucose tolerance and previously undiagnosed diabetes.The mean age of patients was 54 years (range, 26 to 82 years); 52.7% of patients were women. Glucose tolerance testing found that 12.7% of patients had impaired glucose tolerance and 4.8% had previously undiagnosed diabetes. Multivariable-adjusted mean measures of risk factors and odds ratios for obesity, elevated waist-to-hip ratio, hypertension, low levels of high-density lipoprotein cholesterol, elevated triglyceride levels, and hyperinsulinemia showed continuous increases across the spectrum of nondiabetic glucose tolerance. Although a threshold effect near the upper range of nondiabetic glucose tolerance could not be ruled out for triglyceride levels in men and for insulin levels 2 hours after oral challenge in men and women, no other metabolic risk factors showed clear evidence of thresholds for increased risk.Metabolic risk factors for type 2 diabetes mellitus and for cardiovascular disease worsen continuously across the spectrum of glucose tolerance categories, beginning in the lowest quintiles of normal fasting glucose level.

To determine the appropriate patients, methods, and timing for screening for diabetic retinopathy.Relevant articles were identified through prominent review articles, the authors' files, recommendations from experts, and a MEDLINE search (1986 to the present); additional references were selected from the bibliographies of identified articles.Selection of articles on the natural history of retinopathy was limited to large clinical series and formal epidemiologic studies of defined populations. Selection of articles on the therapeutic effect of photocoagulation and of glycemic control was limited to randomized trials. Sources bearing on the accuracy of screening modalities were necessarily more varied.For important variables, individual estimates from multiple studies are presented rather than a single meta-analytic summary estimate.Screening for retinopathy is justifiable if early detection leads to less vision loss at an acceptable cost. The evidence shows that 1) laser therapy reduces the rate of vision loss by 50% among patients with proliferative retinopathy and macular edema, conditions that are often asymptomatic; 2) duration of diabetes is the main risk factor for retinopathy; and 3) standard ophthalmoscopic examination has only moderate sensitivity (about 80% in research settings) and specificity (greater than 90% for proliferative retinopathy but lower for macular edema), making seven-field stereophotography a more accurate method. Estimates of cost effectiveness indicate that screening for retinopathy not only saves years of vision but may be cost saving from a societal perspective.Screening for retinopathy in patients with diabetes, and subsequent photocoagulation therapy for those who have high risk macular edema or proliferative retinopathy, is clearly beneficial.

Purpose To assess the usefulness of urine glucose testing, physician-based and self blood glucose monitoring, and assays of glycated hemoglobin in diagnosing and treating diabetes mellitus. Data identification Relevant literature in English from 1957 through early 1988 was identified via textbooks, original research articles, and review and policy papers, supplemented by a computer-based search of the National Library of Medicine MEDLINE database. Study selection Articles were selected because of prominence, based on frequent citation or policy authoritativeness, and relevance to the epidemiologic and clinical constructs of this paper. Results We analyze the epidemiologic studies underlying the higher diagnostic glycemic thresholds for diabetes proposed by the National Diabetes Data Group and we suggest a diagnostic strategy in which glycated hemoglobin may substitute for glucose tolerance testing. Our section on treatment stresses matching the intensiveness of hypoglycemic therapy with the intensiveness of monitoring: emphasizing the role of self blood glucose monitoring. Our findings and recommendations are summarized in the figures and tables. Conclusions Major advances in the diagnosis and management of diabetes have been made in the past 10 years. In particular, an array of epidemiologic studies have provided a logical basis for diagnostic standards, and two new means of assessing glycemia--glycated hemoglobin and self-monitoring of blood glucose--have become widely available. These tests allow more convenient approaches to diagnosis, and provide a fuller description of glycemia, permitting more informed and intensive therapy.

We examined the relative efficacy of two modes of insulin therapy in five patients with insulin-dependent diabetes. Using a crossover protocol, therapy with multiple insulin injections was compared with the use of continuous subcutaneous insulin infusion (pump therapy); both therapies were regulated by home blood glucose monitoring. Although both therapies were equally effective during 2 to 4 days of inpatient management, pump therapy was clearly superior in the outpatient setting. Mean plasma glucose and hemoglobin A1c concentrations and the frequency of hypoglycemic reactions were significantly less with pump therapy despite apparently equal compliance with both therapies. We conclude that in compliant adult patients with type I diabetes continuous insulin infusion is more effective in achieving normalization of plasma glucose concentration than intensified conventional therapy in the outpatient setting. Although these patients found pump therapy preferable to intensive conventional therapy, the superiority of pump therapy is not explained by this bias. Whether these results are applicable in a more standard treatment setting remains to be established.

Study objective To compare the relative efficacy, risks, and benefits of insulin with glyburide in achieving normoglycemia in non-insulin-dependent diabetes mellitus. Design Randomized, double-blind, placebo-controlled trial with a 9-month treatment period. Setting University hospital. Patients Thirty-one patients with non-insulin-dependent diabetes mellitus who did not have normal glucose control with diet alone. Interventions Once-per-day NPH insulin and placebo glyburide, or glyburide and once-per-day placebo insulin injection. Active drug and placebo adjusted in parallel to achieve fasting plasma glucose level less than 6.4 mmol/L (115 mg/dL) without hypoglycemia. Measurements and main results Insulin and glyburide produced similar improvement in fasting blood glucose levels and hemoglobin A1c concentrations, similar frequencies of mild symptomatic hypoglycemia, and similar weight gain despite dietary reinforcement. Triglyceride and cholesterol levels decreased and high-density lipoprotein cholesterol and ratios of high-density lipoprotein to total cholesterol increased in both groups, with a significantly greater improvement in high-density lipoprotein cholesterol and ratio of high-density lipoprotein total cholesterol in patients treated with insulin. Conclusions Therapy with glyburide or once-per-day NPH insulin provides a similar degree of glucose control in patients with non-insulin-dependent diabetes mellitus. Insulin may have a relative advantage in that it is associated with higher levels of high-density lipoprotein cholesterol and a higher ratio of high-density lipoprotein to total cholesterol.

Diabetes mellitus in nonpregnant adults is a chronic affliction that leads to significant vascular and neuropathic disease. Diabetes during pregnancy can lead to perinatal complications. Both of these types of diabetes are common, often asymptomatic, and readily diagnosable by glucose tolerance testing. As a result, screening can identify many previously undiagnosed patients. However there is only limited evidence that screening results in net therapeutic benefit. In the case of gestational diabetes, controlled trials indicate that hypoglycemic therapy decreases the frequency of macrosomia, but has no effect on perinatal mortality. Our analyses indicate that screening for gestational diabetes is a low-cost intervention that produces a small expected benefit. Screening for diabetes in the nonpregnant adult (almost always a type II diabetic) is not recommended, because the link between improving glucose control and reducing diabetic complications is currently too weak. Screening might be reasonable for particular patients, for example, obese persons who would be spurred to lose weight by a demonstration of glucose intolerance. Screening for type I diabetes followed by immunomodulating therapy is still too experimental for confident analysis.

Five intensively treated, insulin-dependent diabetics exercised for 45 minutes after fasting while receiving basal insulin injections. Plasma glucose concentrations remained stable during exercise but then declined, resulting in clinical hypoglycemia 1 to 2 hours later. Efficacies of three pre-exercise snacks in preventing the hypoglycemia were compared in a randomized crossover design. Orange juice, whole milk, and skim milk, each containing 13 g of carbohydrate, all prevented postexercise hypoglycemia. However, the more rapidly absorbed snacks, orange juice and skim milk, caused a greater increase in plasma glucose concentrations and the area under the glucose curve during exercise. From the recognized glucose profiles that occur after consumption of different carbohydrates, snacks as well as exercise and insulin can now be programmed for intensively treated, insulin-dependent diabetics. Because plasma glucose levels remain stable during exercise done after fasting and only fall late after exercise, a "lente" carbohydrate snack, such as whole milk, is an appropriate pre-exercise snack.