Service, F. John

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.

Objective— To confirm insulinoma as the cause of hypoglycemia in a patient with NIDDM and determine the frequency of the co-occurrence of these two conditions. Research Design and Methods— The patient underwent an in-hospital prolonged fast (≤72 h), according to standard protocol, and an ultrasound examination of the pancreas. All cases of histologically confirmed insulinoma at this institution over the period of 1927–1992 were reviewed to determine the prevalence of pre-existent diabetes mellitus. Results— After 10 h of fasting, plasma glucose was low (1.89 mM); plasma insulin (258 pM) and C-peptide (1.39 nM) were elevated in the absence of sulfonylurea in the plasma. An insulinoma detected by ultrasonography was removed surgically with subsequent reoccurrence of insulin-requiring diabetes. Among 313 cases of insulinoma confirmed at this institution, this patient is the only one with pre-existent diabetes mellitus. Conclusions— Insulinoma occurs extraordinarily rarely in patients with pre-existing NIDDM.

Unauthorized self-administration of hypoglycemic agents produces a unique clinical situation. Because the symptoms and laboratory findings are consistent with a functioning adenoma of the pancreas, there is a significant hazard of unnecessary surgery. By appropriate laboratory tests, however, the alert physician may be able to justify suspicion that the disorder is self-induced. Accurate diagnosis may be further facilitated by recognizing certain similarities in these patients. Review of published reports and study of three cases newly presented have revealed these characteristics with enough consistency for proposal of a psychiatric syndrome. In hypoglycemia, factitial causation is suggested by the combination of female sex, single status, medical knowledge derived from experience as a diabetic or from vocational or family contacts, and features of the hysterical personality.

AbstractInsulinoma in patients with multiple endocrine neoplasia (MEN) is a rare condition that because of its usual multicentricity presents difficulties not encountered in sporadic patients. In contrast to gastrinoma, which is the most common pancreatic neoplasm associated with MEN I, malignancy and duodenal tumors are much less common for patients with insulinomas, and excellent palliative medication is not available. Accordingly, there is a much greater reliance on surgical therapy for this group of patients. Between 1970 and 1991 a total of 19 patients had surgical treatment of MEN I‐related insulinoma. Each patient had hyperinsulinemic hypoglycemia. One patient, with extensive metastases, had unresectable disease. Of the remaining 18, there were 16 (89%) multiple pancreatic tumors. Tumors were located in the neck, body, or tail in 17 cases, 10 of whom also had tumors in the head. Pancreatic resections performed were 1 total, 12 subtotal (7 also had enucleation of tumors from the pancreatic head), and 5 limited distal resections and/or enucleation (conservative resection). There was no operative mortality. One patient developed pancreatitis, fistula, and diabetes following subtotal resection and enucleation. Postoperative cure was achieved in 17 of 18 cases. Recurrent disease occurred in 2 of 5 conservative resections compared to 0 of 12 subtotal resections, with median follow‐up times of 10.4 and 10.3 years, respectively. During the follow‐up period, four patients died, possibly all due to MEN I‐related conditions. Hyperinsulinism in MEN I is associated with the occurrence of multiple, usually benign, pancreatic islet cell tumors, and surgery is an effective treatment modality. Surgical management should be guided by two principles: total removal of gross disease and safe prophylactic pancreatic resection. Acceptable morbidity, low recurrence rates, and a low risk of inducing diabetes lead us to recommend routine subtotal distal pancreatectomy. Meticulous evaluation of the pancreatic head using intraoperative ultrasonography to locate tumors and to locate the pancreatic duct, followed by precise enucleation of residual tumors, is essential to ensure cure.