Sean F. Dinneen

Failure of glucagon suppression contributes to postprandial hyperglycaemia in IDDM

SummaryCarbohydrate ingestion results in a fall in glucagon concentration in non-diabetic but not in diabetic individuals. To determine if, and the mechanism by which, lack of postprandial suppression of glucagon contributes to hyperglycaemia, nine subjects with insulin-dependent diabetes mellitus (IDDM) ingested 50 g of glucose containing both [2-3H] glucose and [6-3H] glucose on two occasions. [6-14C] glucose, insulin and low-dose somatostatin were infused intravenously at the same rates on both occasions. A basal glucagon infusion was started either at the same time (“constant glucagon”) or 2 h following (“suppressed glucagon”) glucose ingestion. This resulted in lower (p<0.001) glucagon concentrations during the first 2 h of the suppressed than during the constant glucagon study days (63±1 vs 108±2 pg/ ml). Lack of suppression of glucagon led to higher (p<0.01) postprandial glucose concentrations (10.3±0.9 vs 8.1±0.7 mmol/l) and a greater (p<0.02) integrated glycaemic response. The excessive rise in glucose was due to higher (p<0.02) rates of postprandial hepatic glucose release during the constant than during the suppressed glucagon study days, whether measured using either [6-3H] glucose (2.6±0.2 vs 2.0±0.2 mmol·kg−1 per 6 h) or [2-3H] glucose (3.0±0.3 vs 2.4±0.2 mmol·kg−1 per 6 h) as the meal tracer. Glucose disappearance, initial splanchnic glucose clearance and hepatic glucose cycling did not differ on the two occasions. Thus, the present studies demonstrate that lack of postprandial suppression of glucagon, by increasing hepatic glucose release, contributes to hyperglycaemia in subjects with IDDM.

Hyperlipidemia in Patients With Primary and Secondary Hypothyroidism

Hypothyroidism is associated with an increased risk of coronary artery disease. This observation may in part be related to the lipid abnormalities in patients with this condition. The lipid profiles of 268 patients with primary hypothyroidism and 27 with secondary hypothyroidism, who were examined in the Thyroid Clinic at the Mayo Clinic during a 1-year period, were reviewed. Hyperlipidemia was commonly associated with both primary and secondary hypothyroidism. The lipid values decreased with treatment of hypothyroidism. Type IIa hyperlipidemia was the most common lipid abnormality in patients with primary hypothyroidism, whereas type IIb was the most common in those with secondary hypothyroidism. Total/high-density lipoprotein cholesterol and low-density lipoprotein/high-density lipoprotein cholesterol ratios were increased in both male and female patients with primary and secondary hypothyroidism, and they decreased with restitution of the euthyroid state, although this decrease achieved statistical significance only in female patients. Significant associations with total thyroxine were noted for total cholesterol and triglycerides and with thyroid-stimulating hormone (thyrotropin) for total cholesterol and low-density lipoprotein cholesterol. Thus, both primary and secondary hypothyroidism are commonly associated with an atherogenic lipid profile, which improves with replacement of thyroid hormone. Even after restitution of the euthyroid state, however, the lipid profile remains atherogenic in male patients. In comparison with primary hypothyroidism, the lipid profile is more atherogenic in secondary hypothyroidism because of the lower high-density lipoprotein cholesterol levels associated with this condition.

Mechanism of accelerated gastric emptying of liquids and hyperglycemia in patients with type II diabetes mellitus

BACKGROUND & AIMS The roles of hyperglycemia in diabetic gastroparesis and gastric delivery in postprandial hyperglycemia of diabetic patients are unclear. The aims of this study were to assess gastric emptying and its relation to postprandial glucose metabolism in patients with asymptomatic non-insulin-dependent diabetes mellitus (NIDDM) and no autonomic neuropathy and to identify motor mechanisms responsible for any accelerated gastric emptying. METHODS Autonomic function, gastric emptying, postprandial glucose metabolism, and hormone levels (glucagon, insulin, cholecystokinin, glucose-dependent insulinotropic polypeptide, neurotensin, and peptide YY) were assessed in healthy volunteers and patients with NIDDM. In a second study, gastric tone and motility were measured in patients with accelerated gastric emptying and in controls. RESULTS Gastric emptying of solids did not differ in the two groups, but liquids emptied faster in patients with NIDDM (P < 0.02). The rate of entry of ingested glucose into the systemic circulation was similar, but higher postprandial glucagon and lower insulin concentrations led to greater (P < 0.01) postprandial hepatic glucose release. Levels of other enteropeptides, gastric accommodation, and antral motility were similar, but patients with NIDDM had greater proximal gastric phasic contractions than controls (P < 0.05). CONCLUSIONS Excessive hepatic glucose release, not rapid entry of ingested glucose, is the primary cause of postprandial hyperglycemia in patients with NIDDM. Accelerated gastric emptying in patients with nonneuropathic NIDDM is associated with increased proximal stomach phasic contractions.

Effects of Changing Diagnostic Criteria on the Risk of Developing Diabetes

OBJECTIVE The American Diabetes Association (ADA) has recommended that the fasting plasma glucose (FPG) level used to diagnose diabetes be changed from 7.8 mmol/l (the level recommended by the National Diabetes Data Group [NDDG] in 1979) to 7.0 mmol/l. We examined the impact of this change on rates of progression to overt diabetes from different levels of FPG. RESEARCH DESIGN AND METHODS Using the laboratory database of Mayo Clinic, we assembled a cohort of 8,098 nondiabetic Olmsted County residents 40 years of age or older on 1 July 1983. Subjects were followed for a median of 9 years. RESULTS Among 7,567 individuals with follow-up FPG data, 778 (10.3%) progressed to ADA diabetes and 513 (6.8%; P < 0.0001) progressed to NDDG diabetes. The risk of developing ADA diabetes was 7, 19, and 39% for individuals with initial FPG values in the ranges of <5.6, 5.6–6.0, and 6.1–6.9 mmol/l, respectively. For progression to NDDG diabetes, the respective risks were 3, 11, and 25%. A clear gradient of risk was observed within the “normal” range of FPG (<5.6 mmol/l). Among the 793 individuals who developed ADA diabetes, 222 (29%) developed NDDG diabetes simultaneously and 291 (37%) developed NDDG diabetes later. In all FPG subgroups, progression to ADA diabetes occurred ∼7 years sooner than progression to NDDG diabetes. CONCLUSIONS The baseline level of FPG is a major predictor of an individuals risk of developing diabetes. The proposed change in the diagnostic criteria for diabetes will lead to earlier diagnosis among individuals who are destined to develop the disease.

Glycaemic control of Type 1 diabetes in clinical practice early in the 21st century: an international comparison

Improving glycaemic control in people with Type 1 diabetes is known to reduce complications. Our aim was to compare glycaemic control among people with Type 1 diabetes using data gathered in regional or national registries.

Impact of a Diabetes Electronic Management System on the Care of Patients Seen in a Subspecialty Diabetes Clinic

OBJECTIVE To compare the compliance with diabetes care performance indicators by diabetes specialists using a diabetes electronic management system (DEMS) and by those using the traditional paper medical record. RESEARCH DESIGN AND METHODS A DEMS has been gradually introduced into our subspecialty practice for diabetes care. To assess the value of this DEMS as a disease management tool, we completed a retrospective review of the medical records of 82 randomly selected patients attending a subspecialty diabetes clinic (DC) during the first quarter of 1996. Eligible patients were defined by the suggested criteria from the American Diabetes Association Provider Recognition Program. During the first quarter of 1996, ∼ one half of the providers began using the DEMS for some but not all of their patient encounters. Neither abstractors nor providers were aware of the intent to examine performance in relationship to use of the DEMS. RESULTS Several measures were positively influenced when providers used the DEMS. The number of foot examinations, the number of blood pressure readings, and a weighted criterion score were greater (P < 0.01) for providers using the DEMS. There was evidence, although not statistically significant, for lower mean diastolic blood pressures (P = 0.043) in patients and for number of glycated hemoglobins documented (P = 0.018) by users of the DEMS. CONCLUSIONS Performance and documentation of the process of care for patients with diabetes in a subspecialty clinic are greater with the use of a DEMS than with the traditional paper record.

Review Paper: Basic Concepts to Novel Therapies: A Review of the Diabetic Foot:

Diabetes mellitus is a global epidemic. Peripheral neuropathy and peripheral vascular disease are complications of diabetes mellitus and the primary causative factors for foot ulceration. Foot ulceration is the leading cause of hospitalization in people with diabetes mellitus. The burden of foot ulceration on health care systems and individual patients is immense. Despite conventional treatment, there persists a high incidence of amputation. A multidisciplinary approach is required to prevent ulcers. This review describes the etiology and risk factors for diabetic foot ulceration and a system for evaluating the diabetic foot. The assessment of neuropathy and the grading of foot ulcers are critically examined. This is important to allow for standardization in clinical trials. The management of diabetic foot syndrome is reviewed. The treatments to ensure vascular supply to the lower limb and control of infection as well as novel therapies, which are becoming available to treat nonhealing, “no-option” diabetic ulcers, are discussed.

Absolute level and rate of change of albuminuria over 1 year independently predict mortality and cardiovascular events in patients with diabetic nephropathy

Aims To determine the nature of the association between baseline albuminuria and risk of all‐cause mortality and cardiovascular disease, and to determine if the rate of change of albuminuria from baseline over 1 year predicts these endpoints in patients with diabetic nephropathy.

The Role of Growth Hormone in the Development of Diabetic Retinopathy

OBJECTIVE To determine the role of growth hormone (GH) in the development of diabetic retinopathy. RESEARCH DESIGN AND METHODS Medical records of 1,423 patients who had undergone insulin tolerance tests (1976–1991) at the Mayo Clinic were examined, and diabetic subjects were identified as either GH-deficient (GH increment after hypoglycemia <5 μg/L and peak <10 μg/L) or GH-suificient. Prevalence of retinopathy was determined in these cases and in a cohort group of diabetic subjects selected to match the GH-deficient cases. These control patients (32 cases) were selected from medical records of individuals who had received medical care at Mayo during the same interval but who had not undergone insulin tolerance testing. RESULTS Twenty-four patients with diabetes were identified, of whom 16 were GH-deficient and 8 GH-sufficient. Despite comparable age, duration of diabetes, and metabolic control, the prevalence of diabetic retinopathy in the GH-deficient group (2 of 16; 12.5%) was less (P < 0.05) than that observed in the GH-sufficient group (5 of 8; 62.5%). Prevalence in the GH-deficient group also was lower than that observed in the cohort control group (15 of 32, 47%). CONCLUSIONS These data strongly suggest that GH contributes to the development of diabetic retinopathy in humans.

Cost-utility analysis in a UK setting of self-monitoring of blood glucose in patients with type 2 diabetes

ABSTRACT Background: Self-monitoring of blood glucose (SMBG) in type 2 diabetes patients has been shown in meta-analyses of randomized trials to improve HbA1c by ∼0.4% when compared to no SMBG. However, the cost of testing supplies is high, improvements in health utility due to improved glycaemic control may be possible and cost-effectiveness has not been evaluated. Methods: A peer-reviewed validated model projected improvements in lifetime quality-adjusted life years (QALYs), long-term costs and cost-effectiveness of SMBG versus no SMBG. Markov/Monte Carlo modelling simulated the progression of complications (cardiovascular, neuropathy, renal and eye disease). Transition probabilities and HbA1c-dependent adjustments came from the United Kingdom Prospective Diabetes Study (UKPDS) and other major studies. Effects of SMBG on HbA1c came from clinical studies, meta-analyses and population studies, but can only be considered ‘moderate’ levels of evidence. Costs of complications were retrieved from published sources. Direct costs of diabetes complications and SMBG were projected over patient lifetimes from a UK National Health Service perspective. Outcomes were discounted at 3.5% annually. Extensive sensitivity analyses were performed. Results: Depending on the type of diabetes treatment (diet and exercise/oral medications/insulin), improvements in glycaemic control with SMBG improved discounted QALYs anywhere from 0.165 to 0.255 years, with increased total costs of £1013–£2564/patient, giving incremental cost-effectiveness ratios of £4508:£15 515/QALY gained, well within current UK willingness-to-pay limits. Results were robust under a wide range of plausible assumptions. Conclusions: Based on the moderate level of clinical evidence available to date, improvements in glycaemic control with interventions, including SMBG, can improve patient outcomes, with acceptable cost-effectiveness ratios in the UK setting.