Is low birth weight a risk factor for the development of diabetic nephropathy in patients with type 1 diabetes? A population-based case-control study.

OBJECTIVES: To investigate if low birth weight as a consequence of intrauterine malnutrition is a risk factor for the later development of diabetic nephropathy. DESIGN AND SUBJECTS: In a case-control set-up a group of type 1 diabetic subjects with diabetic nephropathy (n = 51) and a matched control group with normal kidney function (n = 51) were compared. Diabetic nephropathy and normal kidney function were defined as urinary albumin excretion rate above 200 microg min-1 and below 20 microg min-1, respectively. The birth weights were all obtained from the midwives' original records. SETTING: The patients were identified from a population-based study of chronic diabetic complications in the Funen County, Denmark. MAIN OUTCOMES: Birth weights according to the presence of diabetic nephropathy. RESULTS: The median (10-90 percentile) birth weights were 3,600 g (2,960-4,274) in the group with diabetic nephropathy and 3,600 g (2,880-4,220) in the group without nephropathy, P = 0.52. In the lower quartile of birth weights the median (10-90 percentile) birth weights were 3,000 g (2,780-3,200) in the group with nephropathy versus 2,850 g (2,250-3,175) in the group without nephropathy, P = 0.07. In the upper quartile the median (10-90 percentile) birth weights were 4,225 g (4,000-4,741) in the nephropathy group and 4,000 g in the group without nephropathy, P = 0.13. We found no significant correlation between birth weights and log urinary albumin excretion rate (r = 0.148, P = 0.14) and no difference in the number of patients with nephropathy in the lower versus upper quartiles of birth weights. CONCLUSION: We found no evidence of low birth weight as a risk factor for the development of diabetic nephropathy.

Reference intervals for glucose, beta-cell polypeptides, and counterregulatory factors during prolonged fasting.

To establish reference intervals for the pancreatic beta-cell response and the counterregulatory hormone response to prolonged fasting, we studied 33 healthy subjects (16 males, 17 females) during a 72-h fast. Glucose, insulin, C-peptide, and proinsulin levels decreased (P < 0.001), and the levels of counterregulatory factors increased during the fast [P < 0.05; glucagon and free fatty acids (FFA) with a linear increase and epinephrine, norepinephrine, and cortisol with a clear underlying circadian rhythm]. Growth hormone secretion increased from the first to third day of fasting (P < 0.05) but actually decreased from the second to third day of fasting (P = 0.03). Males had higher glucose and glucagon levels and lower FFA levels during the fast (P < 0.05), whereas no effect of gender on beta-cell polypeptides was observed. A high body mass index resulted in higher insulin and C-peptide levels during the fast (P < 0.05). In conclusion, we have provided reference intervals for glucoregulatory factors during a 72-h fast. We observed a diminished beta-cell response concomitant with an increased secretion of counterregulatory hormones. These results should be of clinical and scientific value in the investigation of hypoglycemic disorders.

[Insulin-dependent diabetes in the county of Funen 1970-2020. An epidemiological description]. / Insulinkraevende diabetes i Fyns Amt 1970-2020. En epidemiologisk beskrivelse.

We present an epidemiological model applicable to insulin-dependent diabetes mellitus (IDDM), based on which prevalence rates are estimated from assumed rates of incidence and mortality of diabetes. The model is illustrated by analysing epidemiological data on IDDM in Fyn County, Denmark for the period 1970-1990, with predictions of prevalence rates during 1990-2020. The epidemiological model assumes known prevalence rates as well as incidence rates and mortality at a given point of time. Under assumed rates of incidence and mortality of IDDM and its complications, the prevalence rate is the dependent variable which is estimated as a function of calendar time. We used epidemiological data on IDDM (operationally defined as insulin-treated diabetes with onset before age 30 years), blindness and nephropathy as well as mortality as reported for the years 1973 and 1987 in Fyn County, Denmark. During 1970-1990 the prevalence of IDDM increased steadily, due to increasing incidence and decreasing risk of complications and mortality. The relative prevalence of patients with nephropathy increased whereas that of blind patients decreased considerably. Under specified assumptions regarding the future levels of incidence of disease, complications and of mortality, it is estimated that the prevalence rate of IDDM in the year 2020 will be 45-60% higher than the level in 1990. The relative prevalence of patients with nephropathy will increase further, whereas the relative prevalence of blind patients will remain constant at a low level. We conclude that IDDM will represent an increasing public health problem in Denmark over the next decades, with increasing overall prevalence rates and a rising proportion of patients with nephropathy. The major determinants of this trend are increasing incidence, combined with declining mortality and declining risk of complications. It is recommended that epidemiological modelling techniques be further developed to provide improved data for the planning of the future diabetes care.

Trends in the epidemiology of IDDM during 1970-2020 in Fyn County, Denmark.

OBJECTIVE: To present an epidemiological model applicable to diabetes based on which prevalence rates are estimated from assumed rates of incidence and mortality of diabetes. Furthermore, this study illustrates the model by analyzing epidemiological data on IDDM in a Danish population during 1970-1990, with predictions of prevalence rates for 1990-2020. RESEARCH DESIGN AND METHODS: The epidemiological model assumes known prevalence rates as well as incidence rates and mortality at a given time. Under assumed rates of incidence and mortality of IDDM and its complications, the prevalence rate is the dependent variable, estimated as a function of calendar time. We use epidemiological data on IDDM (operationally defined as insulin-treated diabetes with onset before age 30 years), blindness, and nephropathy, as well as mortality, as reported for 1973 and 1987 in Fyn County, Denmark. RESULTS: During 1970-1990, the prevalence of IDDM increased steadily because of increasing incidence and decreasing risk of complications and mortality. The relative prevalence of patients with nephropathy increased, whereas that of blind patients decreased considerably. Under specified assumptions regarding the future levels of incidence of disease, complications, and mortality, it is estimated that the prevalence rate of IDDM in the year 2020 will be 45-60% higher than the level in the year 1990. The relative prevalence of patients with nephropathy will increase further, whereas the relative prevalence of blind patients will remain constant at a low level. CONCLUSIONS: IDDM will represent an increasing public health problem in Denmark during the next decades, with increasing overall prevalence rates and a rising proportion of patients with nephropathy. The major determinant of this trend is increasing incidence combined with declining mortality and declining risk of complications. It is strongly recommended that epidemiological models like the one presented here be further developed and implemented at regional levels to provide data for the dimensioning of the current and future diabetes care systems.

[Acute arsenic poisoning]. / Akut arsenforgiftning.

We report three cases of arsenic poisoning in a chemical factory. Three workers were exposed to vinyzene 10,10'-oxydephenarsine and developed mild symptoms of acute poisoning. All patients were treated with dimercaprol, and recovered after a few days. Urine analysis did not show increased arsenic excretion, but this could be due to the large urine samples taken. It is recommended that a urine sample is taken right after admission to hospital and new samples after eight and 16 hours.

Refraction and retinopathy in diabetic children below 16 years of age.

In a population-based cross-sectional study of insulin-dependent diabetes mellitus, 42 children--with a median age of 11 years (range 7-15 years) and a median duration of diabetes of 4 years (range 1-12 years)--underwent an ophthalmological and a biochemical examination (HbA1c). None of the children had visual loss due to diabetes, and only 4.8% had mild, non-proliferative retinopathy. Using cycloplegic refractioning, we found low degree myopia (less than -2D) in 12% of the patients, whereas non-mydriatic measurements increased the frequency of myopia to 29%. We therefore recommend the use of cycloplegia in refractive evaluations of diabetic children.

[Infertility and pregnancy outcome in women with insulin-dependent diabetes. An epidemiological study]. / Infertilitet og graviditetsforløb hos kvinder med insulinafhaengig sukkersyge. En epidemiologisk undersøgelse.

A questionnaire survey comprising an unselected group of 18-49-year old women with insulin-dependent diabetes mellitus and an age comparable control group was performed. Two hundred and forty-five (94%) of the diabetic women and 253 (88%) of the controls answered questions concerning fertility, pregnancy planning and pregnancy outcome. There was no difference in the cumulative rate of pregnancies in the two groups. The prevalence of involuntary infertility among the diabetic women was 17% and similar to that of controls. Compared to controls, diabetic women had significantly fewer pregnancies (mean 1.4 versus 1.7) and fewer births per pregnancy (70% versus 77%), and significantly more diabetic women were nulliparous (48% versus 38%). Only about half of all pregnancies were planned. In general the diabetic women reported that their diabetes had a negative influence on their attitude towards having children.

The relation between retinopathy and albumin excretion rate in insulin-dependent diabetes mellitus. From the Funen County Epidemiology of Type 1 Diabetes Complications Survey.

In a population-based patient material of 138 insulin-dependent diabetics aged 25-34 years, and with a diabetes onset before 30 years of age, the relation between retinopathy and albumin excretion rate was studied. The prevalence rate of any retinopathy was 59% (81) and of proliferative retinopathy 17% (23). After 10 years' duration of diabetes, the prevalence of any retinopathy increased steeply and reached a maximum of about 90% after more than 20 years. Very few patients had proliferative retinopathy during the first 20 years, followed by a gradual increase in prevalence up to 40-50% after 25 years. Twenty-one percent (29) of the study population was found to have an increased urinary albumin excretion rate. These patients were found to have a statistically significant increase in frequency of retinopathy (p < 0.01) -and in particular of proliferative retinopathy -with increasing levels of urinary albumin excretion. Our results suggest a need for more frequent screening for diabetic retinopathy in diabetic patients with than without increased albumin excretion rate.

Increased prevalence of insulin-treated diabetes mellitus in Funen County, Denmark.

OBJECTIVE: To determine the prevalence of insulin-treated diabetes mellitus in Funen County, Denmark as of 1 July 1987 and compare the findings with those of a similar study from 1973. DESIGN: The population was identified by insulin prescriptions collected during a 1 year period. The identity of the prescription holders, the diagnosis and the date of diagnosis were verified from medical records and public registers. RESULTS: The estimated degree of ascertainment of the material is 0.95-0.97. The prevalence rates (per 1000 of the population) of insulin-treated diabetes mellitus as of 1 July 1987 are: 4.74 (95% Cl 4.66-4.82) for all cases, 2.08 (95% Cl 2.01-2.15) for the group with onset of diabetes before age 30 years and 2.66 (95% Cl 2.59-2.73) for the group with onset after age 30 years. These figures correspond to increases of 39, 26 and 51% (P < 0.001) on data collected in 1973. CONCLUSIONS: There was a significant increase in the prevalence of insulin-treated diabetes mellitus in Funen County, Denmark from 1973 to 1987. Analysis of the data shows that an important factor for this increase is a liability to start insulin treatment of type 2 (non-insulin-dependent) diabetes mellitus at an earlier stage than previously. Also, the data suggest that improved prognosis for diabetic patients as well as an increasing incidence of diabetes mellitus are factors involved in the increase.

Segmental tubular sodium reabsorption in type 1 diabetes.

Segmental tubular sodium reabsorption in Type 1 (insulin-dependent) diabetes was measured in 36 patients in a cross-sectional study including one group (n = 13) without significant albuminuria (UalbV < 30 mg 24 h-1), one group (n = 16) with albuminuria in the range from 30 to 300 mg 24 h-1, and a group (n = 7) with nephropathy (UalbV > 300 mg 24 h-1). Lithium clearance was used to measure end proximal delivery. From end proximal delivery, 51Cr-EDTA clearance (GFR) and sodium clearance, segmental tubular reabsorption was calculated. For all patients, GFR was directly correlated with end proximal delivery (r = 0.62, p < 0.0005), while end proximal delivery was inversely correlated to fractional proximal reabsorption (r = -0.71, p < 0.0005). In the subgroup with UalbV less than 30 mg 24 h-1, the direct correlation between GFR and end proximal delivery was also significant (r = 0.77, p < 0.05). In the group with nephropathy (UalbV > 300 mg 24 h-1), mean GFR and end proximal delivery were decreased and fractional proximal reabsorption was increased, but there was still a positive correlation between GFR and end proximal delivery (r = 0.75, p < 0.05) and an inverse correlation between end proximal delivery and fractional proximal reabsorption (r = -0.85, p < 0.05). It is concluded that in these groups of diabetic patients the end proximal delivery is increased while GFR is increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Contraception in women with IDDM. An epidemiological study.

OBJECTIVE: To study whether suitable contraceptive methods to women with diabetes mellitus in fact are applied. RESEARCH DESIGN AND METHODS: A questionnaire survey on the use of contraceptives in all 18-to-49-yr-old women (n = 261) with IDDM in Funen County, Denmark, and an age-comparable control group, (n = 287) was performed. Data were collected from 1987 to 1990. Response was achieved from 94% diabetic women and 88% control subjects. RESULTS: The overall use of contraception in diabetic women (77.1%) was almost identical to that of control subjects (73.6%). Compared with control subjects, significantly fewer diabetic women were using the OCP (P < 0.005) and partner sterilization (P < 0.05), whereas more diabetic women were sterilized (P < 0.0005). Among diabetic contraceptive users, the IUD, female sterilization, condoms, and the OCP each accounted for roughly 20%. Diabetic women using the OCP were predominantly young, and most had never been pregnant; approximately 20% of them used high-dose formulations. Sterilization was frequently used by older diabetic women, and most of these women had 2 or more children; 27% of the diabetic women using an IUD were nulligravidae. Further, 18% used a method with an unsuitable high failure rate. CONCLUSIONS: Our study demonstrates that diabetic women are not sufficiently advised concerning use of contraception.

Epidemiology of menarche and menstrual disturbances in an unselected group of women with insulin-dependent diabetes mellitus compared to controls.

To describe the age at menarche and the prevalence of menstrual disturbances in an unselected group of women with insulin-dependent diabetes mellitus compared to controls, we identified all women having debut of diabetes mellitus before the age of 30 yr and living in the County of Funen, Denmark on July 1, 1987 and being between 18 and 49 yr old. The women received a structured questionnaire inquiring information concerning menstrual conditions. An age comparable group of nondiabetic women was used as controls; 245 (94%) diabetic women and 253 (88%) controls answered the questionnaire. Among women with debut of diabetes before the age of 10 yr, the age at menarche was delayed 1 yr when comparing to controls (P less than 0.0001). During the past 6 months before answering the questionnaire, 8.2% of the diabetic women and 2.8% of the controls had experienced episodes of secondary amenorrhea (P less than 0.01). Corresponding figures for oligomenorrhea were 10.6% and 4.8% (P less than 0.02), for polymenorrhea 7.3% and 5.2% (NS), and for all types of menstrual disturbances 21.6% and 10.8%, respectively (P less than 0.005). Episodes of secondary amenorrhea occurring more than 6 months before answering the questionnaire had been experienced by 10.7% of the diabetic population vs. 4.8% of the controls (P less than 0.05); corresponding figures for primary amenorrhea were 4.9% and 1.2%, respectively (P less than 0.05). We conclude that the age at menarche among women having developed insulin-dependent diabetes mellitus before the age of 10 yr was delayed by 1 yr when compared to controls. The overall prevalence of menstrual disturbances is increased in diabetic women compared to nondiabetic controls.

Infertility and pregnancy outcome in an unselected group of women with insulin-dependent diabetes mellitus.

OBJECTIVES: The null hypothesis of this study is that infertility and pregnancy outcomes in women with insulin-dependent diabetes are identical to those of nondiabetic control subjects. STUDY DESIGN: A questionnaire survey comprising an unselected population of 18- to 49-year-old diabetic women and a comparable control group was performed. Reply rates were 94% (n = 245) and 88% (n = 253), respectively. RESULTS: Cumulative rates of pregnancies and involuntary infertility (17%) did not differ between the two groups. Diabetic women had significantly fewer pregnancies (1.4 vs 1.7) and fewer births per pregnancy than controls, and more diabetic women were nulliparous (48% vs 38%). Half of all diabetic pregnancies were planned. Diabetic women reported that their diabetes had a negative influence on their attitude toward having children. CONCLUSION: In insulin-dependent diabetic women the ability to conceive is normal, but diabetic women have fewer pregnancies and fewer births per pregnancy than controls.

Visual acuity and refraction in type I diabetic patients aged 25-34 years.

Of the total population of 270 25- to 34-year-old insulin dependent diabetic patients with onset less than or equal to 30 years in the county of Fyn, Denmark, a sample of 138 was drawn for examination. Of the 138 examined patients, 4 (2.9%) were legally blind and 119 (86.2%) had good vision in both eyes. The cause of reduced vision was proliferative retinopathy in the majority of eyes. Refraction, measured objectively with a refractometer in cycloplegia and transformed to spherical equivalents, was -0.25 D or more myopic in approx. 50% of eyes. Correlation analyses did not demonstrate significant association between refraction, and duration of diabetes or Hb-A1c.

Comparison of overnight, morning and 24-hour urine collections in the assessment of diabetic microalbuminuria.

With the aim of comparing different urine collection periods in the assessment of micro-albuminuria, urinary albumin excretion rates (AERs) were measured in samples from 24 h, overnight, and morning urine collections in 54 patients aged 17 to 62 years with insulin-dependent diabetes mellitus with a mean duration of 15 years. The AER in overnight urine was found to be reduced by 25% compared to the rate in 24 h and morning urine. Assessing the ability to predict a 24 h AER within the microalbuminuric range (20-200 micrograms/min) we found a sensitivity of 90% and a specificity of 88% for both overnight and morning urine samples. These values were slightly improved by relating AER to the excretion of creatinine and it is concluded that overnight as well as morning urine collections can be used when diagnosing microalbuminuria in insulin-dependent diabetics. Furthermore the results show that the albumin to creatinine ratio in morning urine is a reliable estimate of 24 h AER and better than measurement of the albumin concentration alone.

Effects of cisapride on gastroparesis in patients with insulin-dependent diabetes mellitus. A double-blind controlled trial.

Fourteen insulin-dependent diabetics with symptoms and signs of delayed gastric emptying were treated with a new prokinetic agent, cisapride. In a placebo-controlled cross-over trial no significant differences from placebo was found regarding overall symptomatic effects and effects on gastric emptying of a mixed solid/liquid isotope marked test meal. Solid emptying was most markedly delayed in diabetics compared with healthy controls, but the emptying rate was not correlated to the severity of symptoms as observed for liquid emptying. During active treatment with cisapride the amelioration of symptoms was correlated to increased emptying rates assessed by combined measure of liquid/solid gastric emptying.

Prediction of the course of Graves' disease after medical antithyroid treatment.

The course of thyrotoxicosis in 33 patients with Graves' disease was evaluated clinically and biochemically (free thyroxine index, serum triiodothyronine, thyroid stimulating antibodies, (TSAb), thyroid stimulating hormone binding inhibiting immunoglobulins (TBII)). Relapse of the disease was found to be correlated to anamnestic information of thyrotoxicosis among first degree relatives (predictive value 90%) and to concomitantly raised levels of TSAb and TBII at the start of treatment (predictive value 71%). Mean duration of treatment of patients with long-lasting remission was 16.8 months. When comparing various information used to predict relapse of Graves' disease, anamnestic information of familial predisposition to thyrotoxicosis carries the highest predictive value.