Citations

Both basal and postprandial pancreatic polypeptide (PP) concentrations were exaggerated twofold in lean NIDDM patients, whereas they were normal in lean IDDM and obese NIDDM patients who were hyperglycemic as a result of partial insulin withdrawal. Insulin infusion from an artificial endocrine pancreas, which resulted in fasting euglycemia and near-normoglycemia postprandially, had no effect on PP responses in any of the diabetic patients. No postprandial PP responses were observed in totally pancreatectomized (TPX) patients. Excessive basal and postprandial concentrations of PP in diabetes appear to be related to both leanness and residual beta cell function and, therefore, potential markers for lean NIDDM.

Since little is known regarding the appropriate time for preprandial insulin administration, we compared the effects of 30-min subcutaneous insulin infusions started 60 min, 30 min, and immediately before meal ingestion on postprandial plasma glucose and insulin profiles in eight subjects with insulin-dependent diabetes mellitus. Of these three regimens, administration of insulin 60 min before meal ingestion provided plasma glucose and insulin profiles closest to normal and permitted less insulin to be used. Our results suggest that adjustments in the timing as well as in the amount of insulin administered preprandially may be used in the management of diabetes and that prolonging the interval between administration of insulin and meal ingestion may reduce insulin requirements and thus decrease the hyperinsulinemia usually associated with insulin therapy.

Glucagon normally plays a primary role in promoting glucose recovery from insulin-induced hypoglycemia. Epinephrine compensates largely for deficient glucagon secretion. Glucose recovery from hypoglycemia fails to occur only in the absence of both glucagon and epinephrine. Perhaps as a relatively early feature of autonomic neuropathy, patients with insulin-dependent diabetes mellitus commonly have blunted or absent glucagon secretory responses to hypoglycemia. However, this deficient response is commonly compensated for by epinephrine and glucose recovery occurs. In some patients, progression of adrenergic neuropathy to the point of deficient epinephrine secretory responses to hypoglycemia, coupled with deficient glucagon responses, leads to frequent, severe, and prolonged hypoglycemia. Thus, these glucose counterregulatory systems are of critical importance to patients with insulindependent diabetes mellitus. The efficacy of glucose counterregulation in a given patient may determine the degree to which euglycemia can be achieved with aggressive insulin therapy in that patient.

Although initial laboratory studies using biosynthetic human insulin (BHI) indicate little difference in the intrinsic potency of biosynthetic human and purified pork insulin (PPI) in vitro, certain in vivo observations suggest that BHI may differ pharmacokinetically from pork insulin. If further studies support these suggestions, the use of BHI may be able to provide better glycemic control and more near normal plasma insulin profiles during treatment of insulin-dependent diabetes than can be achieved with presently available insulin preparations. However, BHI appears to offer no advantage over presently available PPI in terms of prevention and treatment of insulin lipodystrophy, insulin allergy, and immune insulin resistance.

To assess the feasibility of preprogramming an open-loop device with insulin flow rates generated by the Biostator Glucose Controller, comparisons were made in 10 juvenile-onset diabetic patients between meals of equal size and composition taken in the morning, at noon, and in the evening and a bedtime snack during a 24-h period of Biostator glucose control. Four additional diabetic patients had Biostator glucose control for 72 h. Similar amounts of insulin were infused for the meals taken at differing times of the day and, except for the morning meal, for the same meal on two successive days. The meal-related glycemic patterns expressed as mean indices of meal excursions (MIME) were similar for meals of identical size and composition during a single day and for the same meal taken on two consecutive days. Preliminary results using an open-loop device preprogrammed by the Biostator system, although encouraging, underscore the deficiency of the subcutaneous route viz. the delayed entry of insulin into the circulation in achieving normal glucose levels and patterns.

Glucose homeostasis in healthy subjects is characterized by postmeal glucose increases of about 40 mg/dl, peaks at about 45 min, decreases close to antecibal levels 1 h after the peak, and no spontaneous oscillations until the next meal. Diabetes is characterized by progressive loss of glucose homeostasis from stable to unstable, which is directly proportional to loss of insulin secretory reserve. Degree of instability of diabetes in ambulatory subjects within a 24-h period can be expressed as mean amplitude of glycemic excursion of M-value and between two successive 24-h periods as mean of daily differences of blood glucose. Stable diabetic persons have lower values, which are closest to those of nondiabetic persons, and unstable diabetic persons have higher values. The mean diurnal blood glucose level is a measure of glycemic control. The failure to restore glycemic patterns of diabetic to those of nondiabetic persons is largely due to the failure of subcutaneously administered insulin to mimic the pattern of insulinemia of healthy subjects.

OBJECTIVE: Chronic hyperglycemia relates to the occurrence of diabetic polyneuropathy (DPN), but has not yet been shown to relate to its overall severity In addition, the degree and duration of hyperglycemia, which measure of chronic hyperglycemia is most predictive of defined levels of severity of DPN, and which other putative risk factors are involved remain unknown. RESEARCH DESIGN AND METHODS: In a longitudinal study of 264 diabetic individuals in Rochester, MN, risk factors and other diabetic complications assessed at regular intervals during an average of approximately 7 years were tested for their association with a composite score of severity of DPN at the last examination. RESULTS: In multivariate analysis, diabetic retinopathy severity level (at last examination), mean ln(24-h proteinuria x duration of diabetes), and mean GHb were the main covariates for severity of DPN (R2 = 0.33). Excluding markers of microvessel and macrovessel disease, the independent risk factors were mean In(GHb x duration of diabetes), GHb, and type of diabetes (R2 = 0.23). CONCLUSIONS: We found that diabetic microvessel disease, chronic hyperglycemia exposure, and type of diabetes are associated with severity of DPN, and we believe these factors are implicated in its cause. Each of the five markers of microvessel disease was a strong covariate for severity of DPN. Mean GHb predicts severity of DPN better than duration of diabetes, and the latter predicts severity of DPN better than mean fasting plasma glucose. Knowing the severity of microvessel disease, the degree of chronic hyperglycemia exposure, and the type of diabetes provides useful information to evaluate whether a coexisting polyneuropathy and its severity is probably due to diabetes.

OBJECTIVE Using a novel minimally invasive (≤ 1.4 mm) technique to sample minuscule (0.5 microliter) amounts of dermal interstitial fluid (ISF), we assessed the accuracy of its glucose concentrations in predicting concurrently measured venous plasma and capillary plasma glucose concentrations. RESEARCH DESIGN AND METHODS A total of 67 adult (37 male and 30 female) volunteers (57 with and 10 without diabetes) with venous plasma glucose levels from 1.6 to 28.4 mmol/l underwent forearm ISF, antecubetal venous, and fingertip capillary sampling. RESULTS Rank correlations were 0.974 for ISF 1 vs. 2, 0.954 for ISF vs. venous, 0.935 for ISF vs. capillary, and 0.987 for venous vs. capillary. Median absolute differences were 0.53 mmol/l for ISF 1 vs. 2, 1.33 mmol/l for ISF vs. venous, 1.06 mmol/l for ISF vs. capillary, and 0.56 mmol/l for capillary vs. venous. Equations expressing ISF glucose as a function of venous and capillary glucose and equations expressing capillary glucose as a function of venous glucose had slopes of 0.995, 0.936, and 1.021, respectively (none significantly different from unity), and intercepts of 1.03 mmol/l (P = 0.024), 0.94 mmol/l (P = 0.131), and 0.56 mmol/l (P = 0.041), respectively. Error grid analysis of ISF vs. venous glucose and of capillary vs. venous glucose showed that 97% of the measurements fell within grids A and B. CONCLUSIONS Dermal ISF sampling is a bloodless minimally invasive technique that provides a medium for glucose measurement, the concentrations of which closely reflect ambient glycemia to a degree comparable with that of capillary glucose measurements.

OBJECTIVE To evaluate both the concordance in the classification of diabetes by clinical and C-peptide criteria and, prospectively, the consistency of the classification by C-peptide. RESEARCH DESIGN AND METHODS Individuals with diabetes who were enlisted in the prospective epidemiological study of diabetic neuropathy (Rochester Diabetic Neuropathy Study [RDNS]) were classified clinically by National Diabetes Data Group (NDDG) criteria to IDDM and NIDDM at entry to the study. In addition, C-peptide response to 1 mg glucagon was measured at entry for the classification to IDDM (basal C-peptide, < 0.17 pmol/ml; increment above basal, < 0.07 pmol/ml) and NIDDM (all other responses) and for concordance with the clinical classification made. The consistency of the C-peptide response was assessed every 2 years for up to 8 years. RESULTS Among 346 individuals with diabetes, 84 were classified as IDDM and 262 as NIDDM by clinical algorithm. COncordance with the C-peptide response occurred in 89% of the patients and remained consistent during 8 years of follow-up. Among the 37 patients with discordant clinical and C-peptide classification, those considered clinically to have NIDDM had a consistent IDDM C-peptide response during follow-up, and most of those considered to have IDDM clinically eventually showed an IDDM C-peptide response during follow-up. CONCLUSIONS Clinical criteria for the classification of diabetes are highly correlated with the assessment of insulin secretory reserve. A small number of individuals considered to have NIDDM clinically or by C-peptide have or develop an IDDM peptide response.