Time Of Diabetes Onset Research Articles

Impact of COVID-19 infection on the development of type 1 diabetes mellitus in children and adolescents

Children did not escape the COVID-19 pandemic. Although, in general, the course of viral infection in children is mild, the question of the long-term effects of COVID-19 on a child and adolescent, in particular, on pancreatic beta cells, remains unclear.Аim: Тo study the characteristics of children with diabetes mellitus identified after COVID-19 infection.Materials and methods: This article presents the preliminary results obtained from children and adolescents hospitalized at the RSSPMCE clinic with the newly diagnosed diabetes mellitus after COVID infection, as well as a systematic review of 61 clinical cases (case series study).Results: Of the 120 children hospitalized at the RSSPMCE clinic with newly diagnosed diabetes, 15 were diagnosed with diabetes after COVID-19 infection, all in a state of diabetic ketoacidosis. Only 20% of children knew about the previous COVID-19 infection, the course of the disease was mild, in 80% of children the infection was asymptomatic. At the time of diabetes onset, all children had a high level of HbA1c - above 10%, a low level of vitamin D, high levels of antibodies to SARS-CoV-2 (IgG), and the need for insulin was above the average.Conclusion: The SARS CoV-2 virus could be the direct cause of the development of diabetes mellitus in children, even with the asymptomatic course of the viral infection. However, the question remains about the exact classification of diabetes after COVID-19 in children. It is necessary to inform the population about the first signs and symptoms of diabetes mellitus in order to timely consult a doctor for the diagnosis of diabetes mellitus.

The analysis of Period1 gene expression in vivo and in vitro using a micro PMT system

To detect a small amount of Period1 (Per1) expression, we developed a micro-photomultiplier tube (μPMT) system which can be used both in vivo and in vitro. Using this system, we succeeded in detecting Per1 gene expression in the skin of freely moving mice over 240 times higher compared with that of the tissue contact optical sensor (TCS) as previously reported. For in vitro studies, we succeeded in detecting elevated Per1 expression by streptozotocin (STZ) treatment in the scalp hairs at an early stage of diabetes, when glucose content in the blood was still normal. In addition, we could detect elevated Per1 expression in a single whisker hair at the time of diabetes onset. These results show that our μPMT system responds to minute changes in gene expression in freely moving mice in vivo and in mice hair follicles in vitro. Furthermore, Per1 in the hair can be used for a marker of diabetic aggravation.

FREQUENCY AND RISKS OF ADVERSE OUTCOMES ASSOCIATED WITH GESTATIONAL DIABETES MELLITUS IN NEONATES

Gestational diabetes mellitus (GDM) is one of the most common endocrinopathies during pregnancy. The issue on the prevalence of its adverse outcomes depending on the time of diabetes onset – before or during pregnancy – is still remaining unclear. The aim of this study was to determine the prevalence and risk of adverse outcomes associated with GDM in neonates in Poltava region. Materials and methods. We conducted a retrospective study that included 10.025 infants born to primigravidae under 28 weeks. Group I included infants (n = 35) who were born to mothers with GDM, and group II covered infants (n = 82) who were born to mothers with pre-gestational diabetes mellitus (PGDM). The control group included 9908 infants who were born to mothers without diabetes. Results. The risks of neonatal respiratory distress were significantly higher in neonates born to women with PGDM and GDM than in women without diabetes (RR 59.6 (95% CI 39.9-88.9) and RR 81.7 (95% CI 38.1- 175), whereas the risk of asphyxia was higher only in women with GDM (RR 16.4 (95% CI 6.5-41.4). Among the mothers with PGDM and GDM, no significant differences were observed in the number of infants with macrosomia (51.4% and 61.0%), hypoglycemia (37.1% and 31.7%), hospitalization in the intensive care unit (31.4% and 48.8%) and mechanical ventilation (20.0% and 23.2%). Conclusion. Diabetes mellitus is associated with an increased risk of developing maternal and neonatal adverse outcomes. The incidence of preeclampsia, premature birth, neonatal respiratory distress, macrosomia, and the use of mechanical ventilation in infants are the same in mothers with gestational and pre-gestational diabetes mellitus.

Long-term prognosis of type 1 diabetes in relation to the clinical characteristics at the onset of diabetes

IntroductionIt is known that age, the degree of glycemic deterioration and the immune status at the time of the onset of type 1 diabetes (T1DM) are objective factors that can predict the residual B-cell function and the glycemic control 1year after diagnosis. Objective: Evaluation of the long-term prognosis of T1DM in relation to the clinical characteristics at the time of diabetes onset. Methods: An observational retrospective study conducted on 200 patients including all the patients with newly diagnosed T1DM in the period from 2003 to 2013. Results: Fifty-three percent of the studied cohort presented initially by diabetic ketoacidosis (DKA). The current studied cohort showed that younger patients required more insulin during follow-up. Female patients needed higher insulin doses at 8 and 10years after diagnosis, yet no difference among both genders during early years of follow up. Patients presenting with DKA required higher insulin requirements over the first 2years and poor glycemic control. C-peptide levels at diagnosis correlated with insulin requirements during the first 2years. Insulin dose at onset correlated positively with the insulin dose over the entire follow up period. A positive correlation was found between HbA1c at onset and 1, 2 and 4year. Conclusion: Female gender, younger age, presence of DKA, lower C-peptide and higher HbA1c at onset could predict a poor long-term outcome. Identification of factors related to a worse outcome of T1DM at the onset of diabetes might help in selecting those patients who should be given more intensive treatment.

Diabetes Onset at 31-45 Years of Age is Associated with an Increased Risk of Diabetic Retinopathy in Type 2 Diabetes.

This hospital-based, cross-sectional study investigated the effect of age of diabetes onset on the development of diabetic retinopathy (DR) among Chinese type 2 diabetes mellitus (DM) patients. A total of 5,214 patients with type 2 DM who were referred to the Department of Ophthalmology at the Shanghai First People’s Hospital from 2009 to 2013 was eligible for inclusion. Diabetic retinopathy status was classified using the grading system of the Early Treatment Diabetic Retinopathy Study (ETDRS). Logistic and hierarchical regression analyses were used to identify independent variables affecting the development of DR. Upon multiple logistic regression analysis, patient age at the time of diabetes onset was significantly associated with development of DR. Further, when the risk of retinopathy was stratified by patient age at the onset of diabetes, the risk was highest in patients in whom diabetes developed at an age of 31–45 years (odds ratio [OR] 1.815 [1.139–2.892]; p = 0.012). Furthermore, when patients were divided into four groups based on the duration of diabetes, DR development was maximal at a diabetes onset age of 31–45 years within each group. A diabetes onset age of 31–45 years is an independent risk factor for DR development in Chinese type 2 DM patients.

Breast cancer incidence before and after diagnosis of type 2 diabetes mellitus in women

The physiological changes associated with type 2 diabetes mellitus begin before disease onset, yet few have examined the incidence of cancer both before and after diabetes onset. We examined the temporal relationship between diabetes and breast cancer risk. Breast cancer risk was assessed in a retrospective cohort study using patient data from the Marshfield Clinic electronic medical record including 5423 women who developed diabetes between 1 January 1995 and 31 December 2009 (reference date) and 26 346 nondiabetic women matched by age, smoking history, residence, and reference date. Breast cancer risk was assessed before and after reference date, adjusting for matching variables, BMI, insurance status, and comorbidities. Primary outcomes included hazard ratio (HR) and number of women needed to be exposed to diabetes for one additional person to be harmed - that is, develop breast cancer (NNEH). HR for breast cancer before diabetes diagnosis was 1.16 (95% CI 1.03-1.31, P=0.0150) and NNEH was 99 at time of diabetes onset. HR for breast cancer after diabetes diagnosis was not significant at 1.07 (95% CI 0.90-1.28, P=0.422), and NNEH was 350 at 10 years post diabetes onset. Diabetic women are at the greatest increased risk of breast cancer near the time of diabetes diagnosis. The comparative NNEH increased shortly after diagnosis and as the duration of diabetes increased. Breast cancer risk appears to be increased during the prediabetes phase, waning after diagnosis, raising important issues regarding timing of breast cancer prevention interventions in women with diabetes.

IL-2 Immunotherapy Reveals Potential for Innate Beta Cell Regeneration in the Non-Obese Diabetic Mouse Model of Autoimmune Diabetes

Type-1 diabetes (T1D) is an autoimmune disease targeting insulin-producing beta cells, resulting in dependence on exogenous insulin. To date, significant efforts have been invested to develop immune-modulatory therapies for T1D treatment. Previously, IL-2 immunotherapy was demonstrated to prevent and reverse T1D at onset in the non-obese diabetic (NOD) mouse model, revealing potential as a therapy in early disease stage in humans. In the NOD model, IL-2 deficiency contributes to a loss of regulatory T cell function. This deficiency can be augmented with IL-2 or antibody bound to IL-2 (Ab/IL-2) therapy, resulting in regulatory T cell expansion and potentiation. However, an understanding of the mechanism by which reconstituted regulatory T cell function allows for reversal of diabetes after onset is not clearly understood. Here, we describe that Ab/IL-2 immunotherapy treatment, given at the time of diabetes onset in NOD mice, not only correlated with reversal of diabetes and expansion of Treg cells, but also demonstrated the ability to significantly increase beta cell proliferation. Proliferation appeared specific to Ab/IL-2 immunotherapy, as anti-CD3 therapy did not have a similar effect. Furthermore, to assess the effect of Ab/IL-2 immunotherapy well after the development of diabetes, we tested the effect of delaying treatment for 4 weeks after diabetes onset, when beta cells were virtually absent. At this late stage after diabetes onset, Ab/IL-2 treatment was not sufficient to reverse hyperglycemia. However, it did promote survival in the absence of exogenous insulin. Proliferation of beta cells could not account for this improvement as few beta cells remained. Rather, abnormal insulin and glucagon dual-expressing cells were the only insulin-expressing cells observed in islets from mice with established disease. Thus, these data suggest that in diabetic NOD mice, beta cells have an innate capacity for regeneration both early and late in disease, which is revealed through IL-2 immunotherapy.

Glycemic control and insulin requirements in type 1 diabetic patients depending on the clinical characteristics at diabetes onset

Introduction: The long-term prognosis of type 1 diabetes (T1DM) was evaluated in relation to the clinical characteristics at the time of diabetes onset. Patients and methods: We examined retrospectively the clinical and laboratory characteristics present at the time of diagnosis in 301 adult patients (187 men) consecutively admitted to hospital with T1DM onset and evaluated the clinical outcome of T1DM during 6 ± 4.8 years following diagnosis. Results: Women needed a greater insulin dose per kg of body weight over the first 2 years following diagnosis. Younger patients at diagnosis had greater insulin requirements during follow-up. Patients with at least one positive pancreatic antibody needed a greater insulin dose 2 years after diagnosis and developed poorer glycemic control during follow-up than patients with no detectable pancreatic antibodies at onset. Diabetic ketoacidosis at onset was associated with greater insulin requirements over the first 2 years of follow-up and with poorer glycemic control during the course of the illness. C-peptide levels at diagnosis correlated with insulin requirements during the first 2 years of follow-up. Patients with higher HbA1c levels at diagnosis had greater insulin requirements in the first year of follow-up. A correlation was found between the HbA1c levels at the consecutive years of follow-up. Conclusions: Female sex, younger age, humoral pancreatic autoimmunity, diabetic ketoacidosis, lower pancreatic reserve and higher HbA1c levels at onset could predict a poor long-term clinical outcome of T1DM in terms of insulin requirements and glycemic control.

Gut microbiota in children with type 1 diabetes differs from that in healthy children: a case-control study

BackgroundA recent study using a rat model found significant differences at the time of diabetes onset in the bacterial communities responsible for type 1 diabetes modulation. We hypothesized that type 1 diabetes in humans could also be linked to a specific gut microbiota. Our aim was to quantify and evaluate the difference in the composition of gut microbiota between children with type 1 diabetes and healthy children and to determine the possible relationship of the gut microbiota of children with type 1 diabetes with the glycemic level.MethodsA case-control study was carried out with 16 children with type 1 diabetes and 16 healthy children. The fecal bacteria composition was investigated by polymerase chain reaction-denaturing gradient gel electrophoresis and real-time quantitative polymerase chain reaction.ResultsThe mean similarity index was 47.39% for the healthy children and 37.56% for the children with diabetes, whereas the intergroup similarity index was 26.69%. In the children with diabetes, the bacterial number of Actinobacteria and Firmicutes, and the Firmicutes to Bacteroidetes ratio were all significantly decreased, with the quantity of Bacteroidetes significantly increased with respect to healthy children. At the genus level, we found a significant increase in the number of Clostridium, Bacteroides and Veillonella and a significant decrease in the number of Lactobacillus, Bifidobacterium, Blautia coccoides/Eubacterium rectale group and Prevotella in the children with diabetes. We also found that the number of Bifidobacterium and Lactobacillus, and the Firmicutes to Bacteroidetes ratio correlated negatively and significantly with the plasma glucose level while the quantity of Clostridium correlated positively and significantly with the plasma glucose level in the diabetes group.ConclusionsThis is the first study showing that type 1 diabetes is associated with compositional changes in gut microbiota. The significant differences in the number of Bifidobacterium, Lactobacillus and Clostridium and in the Firmicutes to Bacteroidetes ratio observed between the two groups could be related to the glycemic level in the group with diabetes. Moreover, the quantity of bacteria essential to maintain gut integrity was significantly lower in the children with diabetes than the healthy children. These findings could be useful for developing strategies to control the development of type 1 diabetes by modifying the gut microbiota.

Comparative metabolic physiology of cynomolgus (Macaca fascicularis) and rhesus (Macaca mulatta): The nature of their naturally occurring diabetes and metabolic syndrome

A direct comparison between cynomolgus and rhesus monkeys of the disease, diabetes, as it progresses naturally and spontaneously, has not been previously reported. Because of the importance of nonhuman primate models for the development of therapeutic agents for diabetes and related metabolic impairments, we have compared our two colonies of monkeys, rhesus in the USA and cynos in China to determine similarities and differences in the presentation of diabetes, its natural evolution, and its responses to therapeutic agents. Both are known to frequently and spontaneously develop adult‐onset obesity‐associated diabetes that appears to be the same disease, with the same complications and the same pathophysiology, as seen in humans. Compared to rhesus, cynos weigh approximately 2–3 kg less at the time of diabetes onset, and have lower levels of hyperinsulinemia (~15–20μU/ml) and hypertriglyceridemia (~50 mg/dl), but have similar levels of hyperglycemia, impairment of glucose tolerance, acute and late insulin responses during an IVGTT, reductions in insulin sensitivity (euglycemic clamps), and attenuation of glucose stimulated insulin release (GGI). Similar pharmacological responses to some antidiabetic agents show that they are both valuable models for the evaluation of efficacy in these metabolic diseases.

Time-varying incidence of cancer after the onset of type 2 diabetes: evidence of potential detection bias

Despite the vast body of epidemiological literature on the risk of cancer in people with diabetes, few studies have examined the pattern of cancer risk during different time windows following diabetes onset. The objective of the study was to examine the risks of site-specific cancer in people with incident type 2 diabetes during different time windows following diabetes onset. This was a population-based retrospective cohort study. The study period was 1 April 1994 to 31 March 2006; censoring occurred at 31 March 2006, at death or on departure from British Columbia, Canada. Using linked health databases, we identified incident cohorts with and without diabetes, who were matched by age, sex and index year. Following a minimum 2-year cancer washout period, first site-specific cancers were identified prospectively in both cohorts. Within 3 months following diabetes onset, participants with diabetes had significantly increased risks of colorectal, lung, liver, cervical, endometrial, ovarian, pancreatic and prostate cancers. After the initial 3-month period, the risks for colorectal (HR 1.15, 95% CI 1.05, 1.25), liver (HR 2.53, 95% CI 1.93, 3.31) and endometrial (HR 1.58, 95% CI 1.28, 1.94) cancers remained significantly elevated compared with those without diabetes. The diabetes cohort remained at increased risk of pancreatic cancer in later years, but followed a different pattern: HR 3.71 at 3 months-1 year, 2.94 at 1-2 years, 1.78 at 2-3 years and 1.65 at 3-10 years (p value for all <0.01). After an initial period of elevated risk, men with type 2 diabetes subsequently had a decreased risk of prostate cancer (HR 0.82, 95% CI 0.76, 0.88). People with type 2 diabetes are at increased risk of select cancers; this risk is particularly elevated at the time of diabetes onset, which is likely to be due to increased ascertainment.

5-year follow-up study of C-peptide secretion in newly diagnosed type I diabetics: relations to HLA-phenotype, insulin requirement and metabolic control.

50 HLA-typed insulin-dependent diabetics were studied at the time of diabetes onset and after 1, 2, 3 and 5 years with regard to C-peptide secretion after combined stimulation with glucose and glucagon, insulin requirement and glycaemic control index. The mean decrease of the residual B-cell reserve was observed within two years. C-peptide secretion was correlated with better metabolic control and lower insulin requirement after more than one year of diabetes duration, but had no influence on this at the time of diabetes onset. The C-peptide response sometimes varied between non response and high response in one individual from one investigation to the next. There was no prognostic value of C-peptide secretion at diabetes onset for the further development of B-cell function. We found a significantly longer persistence of B-cell function in patients who were older and in those with mild symptoms at diabetes onset. The presence of HLA B8, DR3 antigens was correlated with severe ketoacidosis at manifestation and a more pronounced destruction of B-cell function.

Culture-independent identification of gut bacteria correlated with the onset of diabetes in a rat model

Bacteria associated with the onset of type 1 diabetes in a rat model system were identified. In two experiments, stool samples were collected at three time points after birth from bio-breeding diabetes-prone (BB-DP) and bio-breeding diabetes-resistant (BB-DR) rats. DNA was isolated from these samples and the 16S rRNA gene was amplified using universal primer sets. In the first experiment, bands specific to BB-DP and BB-DR genotypes were identified by automated ribosomal intergenic spacer analysis at the time of diabetes onset in BB-DP. Lactobacillus and Bacteroides strains were identified in the BB-DR- and BB-DP-specific bands, respectively. Sanger sequencing showed that the BB-DP and BB-DR bacterial communities differed significantly but too few reads were available to identify significant differences at the genus or species levels. A second experiment confirmed these results using higher throughput pyrosequencing and quantitative PCR of 16S rRNA with more rats per genotype. An average of 4541 and 3381 16S rRNA bacterial reads were obtained from each of the 10 BB-DR and 10 BB-DP samples collected at time of diabetes onset. Nine genera were more abundant in BB-DP whereas another nine genera were more abundant in BB-DR. Thirteen and eleven species were more abundant in BB-DP and BB-DR, respectively. An average of 23% and 10% of all reads could be classified at the genus and species levels, respectively. Quantitative PCR verified the higher abundance of Lactobacillus and Bifidobacterium in the BB-DR samples. Whether these changes are caused by diabetes or are involved in the development of the disease is unknown.

Fulminant autoimmune Type 1 diabetes during interferon‐alpha therapy: a case of Th1‐mediated disease?

A case of autoimmune Type 1 diabetes with some unique characteristics developing in a 29-year-old male during treatment with interferon-alpha (IFN-alpha) for chronic hepatitis C virus (HCV) hepatitis is reported. In this patient IFN-alpha treatment was well tolerated and successful in the cure of hepatitis with eradication of HCV infection within 3 months, but at 8.5 months Type 1 diabetes appeared and insulin therapy was started and maintained thereafter. HLA class II molecular typing was determined and retrospective measurement of islet cell (ICA), glutamate decarboxylase (GADA), tyrosin phosphatase IA-2 (IA-2A) and insulin (IAA) antibodies was performed in serum samples obtained before and at 0.5, 1, 2, 3, 4, 5, 6, 8.5, 10 and 13 months after the beginning of IFN-alpha treatment. Complete HLA class II typing was consistent with homozygosity for the HLA DRB *03011, DQA1 *0501, DQB1 *0201 haplotype. All autoantibodies were undetectable prior to IFN-alpha therapy and remained undetectable up to 6 months of treatment; at 8.5 months, at the time of diabetes onset, ICA were detectable at low titre while GADA were present at high titre. Both ICA and GADA persisted at high levels in subsequent samples. IA-2A remained undetectable in all serum samples, while IAA appeared only after treatment with exogenous insulin. This appears to be a case of autoimmune Type 1 diabetes induced by IFN-alpha treatment and developing on a predisposed genetic background with an unusually rapid development of the autoimmune process as reflected by the absence of detectable autoantibodies up to 2.5 months prior to disease onset. In this example of fulminant Type 1 diabetes a pathogenic process unbalanced towards a Th1-mediated autoimmune response is hypothesized. Diabet. Med. 18, 329-332 (2001)

Improved visual function in IDDM patients with unchanged cumulative incidence of sight-threatening diabetic retinopathy.

To evaluate trends in visual acuity and the cumulative incidence of diabetic retinopathy in a clinic-based observational follow-up study. All patients visiting Hvidore Hospital in 1984 whose diagnosis of IDDM had been made before 41 years of age and between 1965 and 1979 (n = 356) were followed until 1994 or until their deaths. All patients were Caucasians and resided in Copenhagen. Patients were divided into three prevalence cohorts based on time of diabetes onset: group A, 1965-1969 (n = 113); group B, 1970-1974 (n = 130); and group C, 1975-1979 (n = 113). Fifteen years after diabetes onset, the visual acuity was significantly improved in patients with increasing calendar year of the disease onset. The median (interquartile range) visual acuity was 1.0 (0.8-1.0), 1.0(0.9-1.0), and 1.0 (1.0-1.0) in groups A, B, and C, respectively (P < 0.01 overall; P = 0.28 for group A vs. group B; and P < 0.01 for group A vs. group C) with 60, 66, and 93 having a visual acuity of 1.0 in groups A, B, and C, respectively. The cumulative incidence (+/-SEM), expressed as a percentage and calculated according to the life-table method, of proliferative retinopathy, maculopathy, and laser-treated retinopathy 15 years after onset of diabetes were, respectively, 13+/-3, 11+/-3, and 12+/-3 in group A; 16+/-3, 12+/-3, and 21+/-4 in group B; 11+/-3, 5+/-2, and 12+/-3 in group C, respectively (NS). The development of proliferative retinopathy was associated with the degree of retinopathy and albuminuria at baseline and the mean HbA1c during follow-up. The study revealed an improvement in visual acuity with increasing calendar year of diabetes onset but an unchanged cumulative incidence of diabetic retinopathy.

Pancreatic expression of B7 co-stimulatory molecules in the non-obese diabetic mouse.

Expression of the co-stimulatory molecule B7-1 (CD80) on pancreatic beta cells can overcome peripheral T cell tolerance in transgenic models of autoimmune disease. This study aimed to determine if aberrant B7-1 or B7-2 (CD86) expression on pancreatic beta cells is involved in the pathogenesis of autoimmune diabetes in non-obese diabetic (NOD) mice. Immunohistochemical analysis of NOD pancreas sections revealed no evidence of B7-1 or B7-2 expression on pancreatic beta cells at any stage prior to the onset of either spontaneously arising or cyclophosphamide-accelerated diabetes. Likewise, the NOD-derived NIT-1 beta cell line did not express surface B7 or B7-1 mRNA either constitutively or following exposure to IFN-gamma and TNF-alpha, two cytokines known to be present in the insulitis lesion of NOD mice, or cAMP which can induce B7-1 expression on B cells. Both B7-1 and B7-2 were, however, highly expressed on the majority of islet-infiltrating inflammatory cells in NOD mice between days 7 and 12 after the administration of cyclophosphamide which results in accelerated beta cell destruction. Likewise B7-1 and B7-2 were extensively expressed on islet-infiltrating cells present at the time of diabetes onset in NOD SCID mice with adoptively transferred diabetes. By immunohistochemistry and flow cytometry, it was determined that the phenotype of B7+ cells in the pancreas of NOD mice 9 days after cyclophosphamide included a mixture of macrophages and both CD4+ and CD8+ T cells. B7-2 was also expressed on islet-infiltrating cells in the spontaneously occurring diabetes of female NOD mice, but the levels of B7-1 expression were low in comparison with the accelerated models of diabetes. RIP-IL-2 transgenic mice, which have extensive islet infiltration but no autoimmune beta cell destruction, also had virtually no B7-1 expression and a minority of B7-2-expressing inflammatory cells. Thus, the activation of beta cell-specific T cells in NOD mice does not appear to be a result of aberrant expression of B7 on the beta cells. Expression of B7-1 and B7-2 on islet-infiltrating cells is, however, associated with autoimmune beta cell destruction, suggesting a role for the B7-CD28 interaction in this process.

Menarche, menstrual cycle and fertility in diabetic patients

From observations of female type I diabetics, we collected data on menarche, menstrual cycle and fertility. 337 women answered our questionnaire which had been published in journals for diabetic patients. The data were correlated with age, diabetes duration, and the onset of diabetes. The mean age at menarche was inversely correlated with the age of the patients; in diabetics it was 0.8-2 years higher than in the population in which diabetes developed after menarche. As compared to a population of non-diabetics we observed an increase in mean age at menarche of 0.4-1.3 years. The increase was most pronounced if diabetes developed between the age of 3-8 years. The prevalence of primary amenorrhoea in diabetics was 3.6%, in the controls and in diabetics with late onset 1.5%. Irregularities of the menstrual cycle were observed more often in diabetics than in the controls. The prevalences of oligomenorrhoea and secondary amenorrhoea were 14 and 7% in the group of patients with diabetes onset before menarche. In the group with late onset of diabetes the prevalence of secondary amenorrhoea was 12%. Irregularities of the menstrual cycle were found more frequently at the time of diabetes onset, although 76% of the patients had not remarked any change in the frequency of menstrual bleedings. With increasing diabetes duration, the frequency of bleedings normalized. 70.5% of the patients aged 35 or more had spontaneous conceptions, 2.1% were sterile. Both values are not significantly different from the data of the control group.(ABSTRACT TRUNCATED AT 250 WORDS)