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In pregnancy, several physiologic changes take place, the sum of which tends to reset the glucose homeostasis in the direction of diabetes. About 1-2% of all pregnant women develop an abnormal glucose tolerance in pregnancy, but most often glucose tolerance returns to normal postpartum. This condition is called gestational diabetes mellitus (GDM). The possibility that glucose tolerance deteriorates in pregnancy because of diabetes-like changes in the secretory function of the endocrine pancreas has been investigated in healthy controls and in normal-weight gestational diabetic subjects. The insulin responses to oral glucose and mixed meals are equally large in these two groups, but the insulin response per unit of glycemic stimulus is significantly lower in the gestational diabetic subjects than in the controls. Diabetes-like changes in glucagon secretion are not observed in either group. Insulin degradation is unaffected by human pregnancy and the proinsulin share of the total plasma insulin immunoreactivity does not increase in pregnancy. Insulin receptor binding to monocytes from normal pregnant women is increased in midpregnancy but is significantly decreased in late pregnancy. No difference in insulin binding (at tracer insulin concentration) to monocytes from healthy pregnant controls and gestational diabetic subjects is found. The insulin concentration necessary to reduce tracer insulin binding by 50% (ID50) is lower in the gestational diabetic subjects diagnosed in late pregnancy than in the pregnant controls. Together, these findings indicate that the number of insulin receptors on monocytes is decreased in GDM at this stage of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

The incidence, sex, seasonal and geographical patterns of juvenile-onset insulin-dependent diabetes mellitus (j.i.d.m.) were studied retrospectively on one third of the Danish population 1970-1974. The j.i.d.m. incidence remained fairly constant during the study period, the average being 13.2 per 100000 per year. The total number of boys exceeded the number of girls by 27%. A marked peak of incidence was found at 12-14 years, earlier for females than for males. A seasonal variation in onset (diagnosis) of j.i.d.m. was observed with the lowest number of new cases in May-July. The j.i.d.m. incidence seemed to show socioeconomic differences, being highest in those parts of the survey area with lower status.

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The objective of the present study was to assess the prevalence of familial aggregation of Type 1 (insulin-dependent) diabetes mellitus among Danish families with a diabetic child aged 20 years or less and to compare epidemiological data for familial and sporadic cases. We attempted to identify all patients with Type 1 diabetes aged 0-19 years in Denmark treated at paediatric departments or at departments of internal medicine. This comprises more than 98% of all patients with Type 1 diabetes in this age group. Patients were identified through the local diabetic out-patient registry and asked to complete a questionnaire regarding data on diabetes onset and family history. Of 1574 probands 1419 agreed to participate (90.2%). Additional cases of Type 1 diabetes were found in 171 families (12.8%). Of these 115 were parent-offspring affected families, and in 56 families at least two siblings had Type 1 diabetes and healthy parents. Significant correlation in age at onset of Type 1 diabetes in concordant siblings was observed (r = 0.5, p = 0.0004). Significantly more probands had an affected father with Type 1 diabetes than a mother affected (p < 0.0001). Heterogeneity in epidemiological characteristics was observed between familial and sporadic cases, i.e. familial index cases were younger at onset of the disease, their parents were younger at birth of the index case, and there was no difference in gender of familial cases in contrast to sporadic cases where significantly more males were found. Over a 4-year period (1986-1989) an increasing trend in incidence was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

The occurrence of organ-specific, cellular hypersensitivity against pancreatic components was examined in twenty-two diabetics by means of the leucocyte migration test. An extract was prepared from pooled porcine pancreatic glands, in which atrophy of the exocrine tissue had been induced by ligation of the pancreatic duct. A specifically altered in vitro reactivity to the pancreatic preparation, consistent with a state of organ-specific, cellular hypersensitivity, was demonstrated in the diabetic group as compared to a control group. Intracutaneous injection of the same preparation in six diabetics with a positive in vitro reaction induced a typical delayed type reaction in four. DIABETES 20: 424-27, June, 1971. The literature on diabetes mellitus from early this century contained sporadic descriptions of mononuclear cell infiltration in and around the islets of Langerhans in the pancreas of patients suffering from diabetes. These reports did not attract much attention until it was later established that round cell infiltration of the endocrine pancreas was a frequent feature especially of infantile diabetes mellitus of short duration. 1 It has been emphasized 2 that the rarity of these histopathological changes is probably more apparent than real, as they are easily overlooked. In a recent, more extensive study, mononuclear cell infiltration, predominantly lymphocytes, could be demonstrated in and around the islets of Langerhans in 68 per cent of patients with juvenile diabetes mellitus of short duration. 3 As a qualitative phenomenon this cellular infiltration and the associated histopathological changes (in juvenile diabetes) cannot be distinguished from the ones found in autoimmune disorders in which organ-specific, humoral and/

It has previously been observed that offspring of mothers with insulin-dependent diabetes mellitus (IDDM) have a lower risk of IDDM than offspring of IDDM affected fathers. To assess the offspring IDDM recurrence risk in a Danish population-based study and to investigate parental and offspring-related biological variables that might influence this risk, we identified 2726 IDDM probands and their 2826 offspring from a background population of 1.725 million people (33% of the Danish population). Current age of probands was 20-65 years and their age at IDDM onset was 30 years or less. Sixty-nine offspring (2.4%) were affected with IDDM. The sex difference in the parental-offspring IDDM transmission rate was confirmed. The cumulative IDDM risk up to age 30 years was found to be significantly decreased in maternal offspring compared to paternal offspring (2.3 +/- 0.6 and 5.7 +/- 0.9 %, RR = 2.40, 95% CI 1.30-4.47; p = 0.004) only if parents were diagnosed with IDDM before birth of the offspring. However, due to the low number of diabetic offspring of probands diagnosed with IDDM after offspring birth, this observation needs to be confirmed in a larger population. In a subpopulation of the 2380 offspring, whose parents were all diagnosed with IDDM before offspring birth, the recurrence risk was significantly increased in offspring of male probands diagnosed up to age 17 years compared to offspring of fathers diagnosed at older ages (8.5 +/- 1.8 and 3.6 +/- 1.0%; RR = 2.27, 95% CI 1.21-4.25; p = 0.006). No such relation was found in maternal offspring. Using the Cox proportional hazards model on this offspring subpopulation we found that paternal age at IDDM onset was the only statistically significant predictor of IDDM recurrence risk. Our findings may be important for counselling families in which one parent has IDDM.

We evaluated the epidemiology of diabetic ketoacidosis in the period 1960-1979. In Frederiksborg County, Denmark, the incidence of ketoacidosis at the county hospital increased from 60 per 100,000 in the period 1943-1963 to 120 per 100,000 in the period 1960-1979. In the investigation period we found an increasing incidence confined to urban areas. Precipitating factors were not somatic in 53% of the cases. Patients in the lowest social class (V) were in a higher risk group, experiencing ketoacidosis more often and having a higher frequency of severe acidosis. Forty-nine percent of the patients have had a diabetes duration of more than 5 yr. The lethality rate decreased from the period 1943-1963 and was 4.7% in the investigation period 1960-1979.