Citations

Of all the known diabetic individuals residing in the community of Rochester, Minnesota, only about one-half would have been recognized through a review of the medical records of 1 yr. Only one-fifth of the diabetic residents were hospitalized during the index year and a similarly small proportion were attended in a diabetes clinic. This selective process produced distortion in the apparent clinical spectrum of diabetes observed at different levels in the medical care system. Notable was overestimation of the relative importance of insulin-dependent diabetes and of the vascular complications of diabetes among hospital and diabetes clinic patients. Referral bias should be taken into account when differences are noted in the epidemiologic features of diabetes as reported from different types of medical care settings.

In a population-based study in Rochester, Minnesota, the clinical characteristics of 1135 patients newly diagnosed with diabetes (1945–69) were compared with those of 810 residents with diabetes mellitus on prevalence day (1 January 1970). The prevalence patients were older and the male:female ratio was reduced from that seen among incidence cases. The prevalence patients were more likely to be on oral agents, had lower fasting blood glucose levels, were less likely to be symptomatic, but were more likely to have macrovascular and microvascular complications. These differences seemed to come about as a result of variation in survival rates among patients with specific characteristics, differential migration of certain groups of patients, and changes in the status of individuals.

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.

The incidence of diabetes mellitus by clinical type was determined for the community of Rochester, Minnesota, 1945–69. Overall adjusted incidence rates per 100,000 person-years were 8.4 for IDDM, 80.1 for obese NIDDM, 45.6 for nonobese NIDDM, and 3.6 for secondary diabetes, using our definitions. Strict use of National Diabetes Data Group criteria would have reduced the apparent incidence of all diabetes by about 20% through the deletion of NIDDM cases. The National Diabetes Data Group classification improved the clinical homogeneity of IDDM patients compared with “juvenile-onset” diabetes but had little effect on NIDDM relative to “maturity-onset” diabetes, since essentially the same patients were included in both groups. Separation of NIDDM into obese and nonobese subcategories accomplished little in the way of defining two more homogeneous subgroups.

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.

Clinical peripheral vascular disease (PVD) was studied in an incidence cohort of 1073 residents of Rochester, Minnesota, who were found to have diabetes mellitus in the period 1945–69. About 8%; of patients already had clinical evidence of PVD at the time of diagnosis of diabetes. The proportion increased with the age at which diabetes was discovered. Among those unaffected initially, the incidence of subsequent PVD was slightly greater for men, 21.3 per 1000 person-years, than for women, 17.6 per 1000, and it increased both with age and duration of diabetes. The cumulative incidence of subsequent PVD was estimated to be 15%; at 10 yr and 45% at 20 yr after the diagnosis of diabetes. The age-adjusted prevalence of residents with diabetes and a history of PVD was 3.3 per 1000 population 30 yr of age or over on 1 January 1970.

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.