The prevalence of clinical diabetic polyneuropathy in Spain: a study in primary care and hospital clinic groups

Summary A multiregional cross-sectional study of clinical diabetic polyneuropathy (DPN) was carried out among Spanish diabetes patients using a standard system for scoring symptoms and signs of polyneuropathy. The main patient sample comprised 2 644 patients (54.7 % women) aged 15–74 years (mean 57.2 ± 0.3 years), 86.9 % of whom had Type II (non-insulin-dependent) diabetes mellitus and 29.4 % were attending hospital clinics. Mean duration of diabetes since diagnosis was 10.2 ± 0.2 years. The prevalence of DPN was 22.7 % (95 % confidence interval 21.2–24.3 %) in the whole sample, 12.9 % (9.4–16.5 %) among patients with Type I (insulin-dependent) diabetes mellitus and 24.1 % (22.4–25.9 %) among patients with Type II diabetes; there was no significant difference in prevalence between men and women. Prevalence increased with age (from < 5 % in the 15- to 19-year-old age group to 29.5 % in the 70- to 74-year-old group) and with duration of diabetes since diagnosis (from 14.2 % among those with duration < 5 years to 44.2 % among those with duration > 30 years). In a supplementary sample of 161 diabetic patients aged 75 to 79 years (excluded from the main sample to prevent confusion between diabetes-induced and ageing-induced neuropathies), prevalence was 37.8 %. Ninety-three patients (3.3 %) had or had had foot ulcers and 21 of these 93 (0.7 %) had undergone amputation; 90.8 % of ulcerated patients had Type II diabetes, and 54 % had DPN (in most cases with loss of perception of vibration), as against a prevalence of DPN of 19.9 % among patients without ulcers. We conclude that nearly a quarter of Spanish diabetic patients have DPN; that over 90 % of DPN patients have Type II diabetes; that the prevalence of DPN increases with age and with the duration of the disease, and that the risk of foot ulcers among DPN patients is about three times the risk among diabetic patients without DPN. We accordingly emphasize the responsibility of primary care physicians to try to prevent diabetic foot lesions by early diagnosis of DPN. [Diabetologia (1998) 41: 1263–1269] Received: 10 March 1998 and in final revised form: 8 June 1998     

Familial Risk of Type I diabetes in European Children

Summary The characteristics of familial Type I (insulin-dependent) diabetes mellitus – that is Type I diabetes in a first degree relative were investigated for children diagnosed before the age of 15 years using data from an international network of population-based registries (the Eurodiab Ace network) and from a case-control study (Eurodiab Ace Substudy 2) conducted by eight of the network's centres. Ecological analysis across the 18 centres showed a positive association between the population incidence rate of Type I diabetes and the prevalence of Type I diabetes in fathers of affected children (Spearman's rank correlation coefficient r _s = 0.70, p < 0.001). A similar association was observed with the prevalence in sibling (r _s = 0.71, p < 0.001), but the association with prevalence in mothers was weaker and not significant. Pooling results from all centres showed that a greater proportion of fathers (3.4 %) of affected children had Type I diabetes than mothers (1.8 %) giving a risk ratio of 1.8 (95 % CI 1.4 to 2.5). Affected girls were more likely to have a father with Type I diabetes than affected boys (odds ratio 1.56, 95 % CI 1.07 to 2.27), but there was no evidence of a similar finding for mothers or siblings. Children with disease onset in the 0–4 year age-range were more likely to have an affected father than were children who were older at onset, and similar although weaker associations were seen in mothers and siblings. This suggests that familial Type I diabetes patients have a younger age at onset than non-familial patients. In conclusion, a positive association between the prevalence of familial Type I diabetes and the population Type I diabetes incidence rate was shown and the characteristics of familial Type I diabetes (younger age at onset and preferential transmission of disease from tather to child and particularly from father to daughter) were described. [Diabetologia (1998) 41: 1151–1156] Received: 16 February 1998 and in revised form: 4 May 1998     

Islet autoantibodies in cord blood from children who developed Type I (insulin-dependent) diabetes mellitus before 15 years of age

Summary Islet autoantibodies are early markers for Type I (insulin-dependent) diabetes mellitus. The aim of this study was to establish whether islet autoantibodies were present at birth in children who developed Type I diabetes before 15 years of age. Cord blood sera from 81 children who developed Type I diabetes between 10 months and 14.9 years of age were tested for glutamic acid decarboxylase autoantibodies (GAD65Ab), islet cell antigen 512 autoantibodies (ICA512Ab), insulin autoantibodies (IAA) all by quantitative radioligand binding assays and islet cell autoantibodies (ICA) by indirect immunofluorescence. Cord blood sera from 320 randomly selected matched children were controls. The children who developed Type I diabetes had an increased frequency of cord blood islet autoantibodies compared with control subjects: Glutamic acid decarboxylase autoantibodies were detected in 6 % (5/81) patients and 2 % (5/320) control subjects (p = 0.03); islet cell antigen 512 autoantibodies in 5 % (4/73) patients and 1 % (4/288) control subjects (p = 0.06); insulin autoantibodies (IAA) in 0 % (0/79) patients and 0.3 % (1/320) control subjects (p = 0.36); and islet cell autoantibodies in 10 % (8/81) patients compared with 0.6 % (2/320) control subjects (p = 0.0001). Taken together, 17 % (14/81) patients had one or more islet autoantibody compared with 4 % (12/320) control subjects (p = 0.0001). Whereas none of the control children had more than one antibody, 4 % (3/81) children who later developed Type I diabetes were double positive (p = 0.002). Although glutamic acid decarboxylase autoantibodies' concentrations in cordblood correlated to those in the mothers' blood at the time of delivery, no corresponding correlation was found for the other two types of autoantibodies. The increased frequency of cord blood islet autoantibodies suggests that the Type I diabetes process could already be initiated in utero. [Diabetologia (1999) 42: 181–187] Received: 20 August 1998 and in revised form: 16 October 1998     

The ‘accelerator hypothesis’: relationship between weight, height, body mass index and age at diagnosis in a large cohort of 9,248 German and Austrian children with type 1 diabetes mellitus

Aims/hypothesis The aim of this study was to investigate whether either increased weight or BMI are associated with the earlier manifestation of type 1 diabetes mellitus in children. Methods We evaluated anthropometric measurements in a large cohort of 9,248 patients of European extraction who were diagnosed in the years 1990–2003 in 116 pediatric clinics throughout Germany and Austria. Results Patients were divided into four groups according to age (0–4.9 years, 5–9.9 years, 10–14.9 years and 15–20 years). Significantly higher standard deviation scores (SDSs) for weight and BMI at diabetes onset were found for both boys and girls in the three younger age groups (up to 14.9 years of age) compared with the reference population (p<0.00001). In addition, the BMI SDS and the weight SDS were significantly higher in the 0–4.9-years age group than in all other groups (p<0.00001), and BMI SDS at onset gradually decreased with increasing age at manifestation (p<0.0001). Over the >10-year study period, there was a continuous rise in the weight-SDS and the BMI-SDS in the cohort (p<0.0001), especially in the 5–9.9-years and the 10–14.9-years age groups. Multivariate analysis revealed a significant influence of male sex and of year of manifestation on BMI SDS (p<0.0001) and demonstrated a negative association between the patients’ BMI SDS and age at diagnosis, with a mean annual decrease in BMI SDS of −0.0248 (95% CI −0.0294 to −0.0202, p<0.0001). Conclusions/interpretation A higher BMI was associated with a younger age at diabetes onset. Increased weight gain could therefore be a risk factor for the early manifestation of type 1 diabetes. Electronic supplementary material Supplementary material is available for this article at and accessible for authorised users.     

Promoter (4G/5G) plasminogen activator inhibitor-1 genotype in Pima Indians: relationship to plasminogen activator inhibitor-1 levels and features of the insulin resistance syndrome

Summary Elevated plasminogen activator inhibitor-1 may contribute to vascular disease in diabetes mellitus. Pima Indians have a low incidence of cardiovascular disease despite having a high prevalence of non-insulin-dependent diabetes mellitus (NIDDM) which in this population is not associated with elevated plasminogen activator inhibitor-1 activity. In Caucasians an insertion/deletion (4G/5G) polymorphism in the promoter region of the plasminogen activator inhibitor-1 gene that has been related to activity levels of its protein in plasma differentially binds repressor and enhancer elements. In 265 Pima Indians (133 diabetic, 132 non-diabetic, 129 male, 136 female, mean age 46.6, range 34–68 years) the promoter genotype frequencies were 23.0 % for 4G/4G, 49.8 % for 4G/5G and 27.2 % for 5G/5G compared to 35.4 %, 50.8 % and 13.8 % respectively (χ² = 15.3, 2 df, p < 0.0005) previously reported in Caucasians with NIDDM. The mean plasma activity levels in the three genotypes in the Pima Indians were 18.2, 19.1 and 18.1 U/ml, respectively. Plasminogen activator inhibitor-1 activities correlated with plasma insulin (r = 0.38, p < 0.0001), body mass index (r = 0.24, p < 0.0001), and with triglyceride level (r = 0.12, p = 0.054) but there was no relationship between promoter genotype and activity. A steeper regression slope between plasminogen activator inhibitor-1 activity and triglycerides has been observed in Caucasians with the 4G/4G genotype as compared to Caucasians with the other genotypes. This was not found in the Pima population which may indicate a functional difference in this gene associated with reduced cardiovascular risk and may be involved in the lack of association of plasminogen activator inhibitor-1 levels with NIDDM in Pima Indians. [Diabetologia (1996) 39: 1512–1518] Received: 7 May 1996 and in revised form: 21 August 1996     

Genetic heterogeneity of autoimmune diabetes: age of presentation in adults is influenced by HLA DRB1 and DQB1 genotypes (UKPDS 43)

Aims/hypothesis. Juvenile-onset, insulin-dependent diabetes is associated with islet cell antibodies and with specific “high-risk” HLA-DRB1 and HLA-DQB1 genotypes. Patients with Type II (non-insulin-dependent) diabetes mellitus can have islet-related antibodies, but the genotypic associations at different ages of onset have not been evaluated. Our aim was to determine (i) the prevalence of DRB1 and DQB1 genotypes in patients at diagnosis of Type II diabetes at different ages from 25 to 65 years compared with the general population, and (ii) whether the presence of islet cell antibodies (ICA) or glutamic acid decarboxylase antibodies (GADA) or both by age is associated with different DRB1 and DQB1 genotypes. Methods. The antibodies to islet cells and those to glutamic acid decarboxylase were measured in 1712 white Caucasian diabetic subjects at diagnosis of diabetes and they were genotyped for HLA DRB1 ^* 03 and DRB1 ^* 04 and the high-risk DRB1 ^* 04-DQB1 ^* 0302 haplotype. To assess over-representation of high-risk alleles for Type I (insulin-dependent) diabetes mellitus, the prevalence of high-risk alleles in diabetic patients was expressed relative to the prevalence of low-risk alleles, non-DR3/non-DR4, that provided a reference denominator in both the diabetic patients and in 200 non-diabetic control subjects. The prevalence of ICA or GADA or both in patients with different HLA genotypes was assessed in those diagnosed in four age groups, 25–34 years, 35–44 years, 45–54 years and 55–65 years. Results. In Type II diabetic patients presenting at ages 25–34, 35–44 and 45–54 years, there was an increased prevalence of DR3/DR4 compared with the general population with approximately 6.5-fold, 2.9-fold, 2.1-fold over-representation, respectively (p < 0.0001, < 0.01, < 0.05) but this was not found in those aged 55–65 years old. In the group aged 25–34 years, 32 % of patients with ICA or GADA or both had DRB1 ^* 03/DRB1 ^* 04-DQB1 ^* 0302 compared with 10 % in those aged 55–65 years and expected 3 % prevalence. Conversely, only 14 % of those aged 25–34 years with antibodies had non-DR3/non-DR4, compared with 35 % in those aged 55–65 years. There was thus pronounced age heterogeneity in DRB1 and DQB1 predisposition to Type II diabetes. The antibodies displaced DRB1 or DQB1 genotypes in the multivariate model for requiring insulin therapy by 6 years of follow-up. Conclusion/hypothesis. The age of presentation of Type I diabetes in adulthood was in part dependent on the DRB1/DQB1 genotype. Islet cell antibodies and glutamic acid decarboxylase antibodies were strongly associated with DRB1 ^* 03/DRB1 ^* 04-DQB1 ^* 0302 in early adulthood but showed little relation with specific HLA genotypes after the age of 55 years. [Diabetologia (1999) 42: 608–616] Received: 27 April 1998 and in final revised form: 20 January 1999     

Record-high incidence of Type I (insulin-dependent) diabetes mellitus in Finnish children

Aims/hypothesis. In Finland, the incidence of Type I (insulin-dependent) diabetes mellitus in children aged 14 years or under is the highest in the world and the trend in incidence has been increasing. Our aim was to determine the most recent trends in incidence and the age distribution at diagnosis of Type I diabetes. Methods. Data on the incidence of Type I diabetes in Finland nationwide were obtained from two sources: for the period 1965 to 1986 from the Central Drug Registry of the Social Insurance Institution and for the period 1987 to1996 from the prospective childhood Type I diabetes registry. The annual incidence was calculated per 100 000 people. The increase and the trend in incidence were estimated by fitting the linear regression model with the annual incidence data. Results. During 1987 to 1993 the incidence of Type I diabetes seemed to be rather stable at 36 per 100 000 per year. The incidence has continued to increase thereafter and reached 45 per 100 000 per year in 1996. The analysis of the long-term trend in incidence between 1965 and 1996 showed an absolute incidence increase of 0.67 per year on average being 3.4 % compared with the incidence in 1965. The increase from 1987 to 1996 was highest in very young children 1–4 years old at diagnosis. Conclusion/interpretation. The high incidence of Type I diabetes in Finnish children has thus far not levelled off but is increasing further. If the trend continues, the predicted incidence in Finland will be approximately 50 per 100 000 per year in the year 2010. [Diabetologia (1999) 42: 655–660] Received: 15 June 1998 and in final revised from: 14 December 1998     

The role of aldose reductase gene in the susceptibility to diabetic nephropathy in Type II (non-insulin-dependent) diabetes mellitus (Short Communication)

Summary The dinucleotide repeat polymorphism (5 ′-ALR2) in the promoter region of the aldose reductase gene on chromosome 7q35 has been implicated in the development of diabetic nephropathy in Type I (insulin-dependent) diabetes mellitus, and markers flanking the aldose reductase locus have given evidence suggestive of a linkage between diabetic nephropathy and Type II (non-insulin-dependent) diabetes mellitus in Pima Indians. To examine whether the 5 ′-ALR2 polymorphism in the aldose reductase gene is involved in the development of diabetic nephropathy in Caucasians with Type II diabetes, we carried out a large association study. Patients with Type II diabetes from one outpatient clinic were screened for diabetic nephropathy and divided into three groups according to the degree of this disease: 179 patients with normoalbuminuria, 225 patients with microalbuminuria and 70 patients with proteinuria. Patients with normoalbuminuria were included in the study only if they had had Type II diabetes for 10 or more years. DNA from all patients was genotyped for the 5 ′-ALR2 polymorphism using a previously established polymerase chain reaction protocol. The frequency of the putative risk allele Z-2 was 34.6 %, 34.2 % and 33.6 % in the normoalbuminuria, microalbuminuria and proteinuria groups, respectively. Similarly no difference among groups was found for the frequency of the putative protective allele Z + 2. In conclusion, the results of our association study in Caucasian patients with Type II diabetes do not support the hypothesis that the 5 ′-ALR2 polymorphism in the aldose reductase gene contributes to susceptibility to diabetic nephropathy. Diabetologia (1999) 42: 94–97 Received: 4 May 1998 and in revised form: 20 July 1998     

Diabetes mellitus and the incidence of hip fracture: results from the Nord-Trøndelag Health Survey

Abstract Aims/hypothesis. To study if people with Type I (insulin-dependent) or Type II (non-insulin-dependent) diabetes mellitus have increased risk of hip fracture. Methods. The study population consisted of 35 444 people 50 years of age and older, attending a health screening in a Norwegian county. They were followed up with respect to hip fracture for 9 years, and 1643 new hip fractures were recorded. Results. The relative risk of hip fracture for women with Type I diabetes compared with women without diabetes was 6.9 (95 % confidence interval 2.2–21.6) adjusted for age, body mass index and daily smoking. The relative risk for men was nearly the same, but not statistically significant. Among women 50–74 years of age with Type II diabetes for more than 5 years, the relative risk was 1.8 (95 % confidence interval 1.1–2.9). This increased risk persisted when insulin-treated women were excluded from the analysis. After additional adjustment for possible medical consequences of diabetes (impaired vision, impaired motor abilities and history of stroke) the relative risk among women 50–75 years of age with Type II diabetes was reduced to 1.5 (95 % confidence interval 0.9–2.5). Conclusion/interpretation. We found an increased risk of hip fracture in women younger than 75 years with Type I diabetes or with Type II diabetes of long duration. In older men, there was an increased risk associated with Type II diabetes of shorter duration. Whether the increased risk is attributed to reduced bone mass or to factors associated with falling has not been determined. [Diabetologia (1999) 42: 920–925] Received: 4 January 1999 and in revised form: 29 March 1999     

Enlarged subcutaneous abdominal adipocyte size, but not obesity itself, predicts Type II diabetes independent of insulin resistance

Aims/hypothesis. Cross-sectional studies indicate that enlarged subcutaneous abdominal adipocyte size is associated with hyperinsulinaemia, insulin resistance and glucose intolerance. To further explore the pathophysiological significance of these associations, we examined prospectively whether enlarged subcutaneous abdominal adipocyte size predicts Type II (non-insulin-dependent) diabetes mellitus. Methods. Body composition (hydrodensitometry), mean subcutaneous abdominal adipocyte size (fat biopsy), insulin sensitivity (hyperinsulinaemic clamp) and the acute insulin secretory response (25-g i. v. GTT) were assessed in 280 Pima Indians with either normal (NGT), impaired (IGT) or diabetic glucose tolerance (75-g OGTT). Subjects with NGT were then followed prospectively. Results. After adjusting for age, sex and per cent body fat, mean subcutaneous abdominal adipocyte size was 19 % and 11 % higher in subjects with diabetes and IGT, compared with those with NGT (p < 0.001). Insulin sensitivity was inversely correlated with mean subcutaneous abdominal adipocyte size (r = –0.53, p < 0.0001), even after adjusting for per cent body fat (r = –0.31, p < 0.001). In 108 NGT subjects followed over 9.3 ± 4.1 years (33 of whom developed diabetes), enlarged mean subcutaneous abdominal adipocyte size but not high per cent body fat, was an independent predictor of diabetes, in addition to a low insulin sensitivity and acute insulin secretory response [relative hazard 10^th vs 90^th centile (95 % CI): 5.8 (1.7–19.6), p < 0.005]. In 28 NGT subjects with a 9 % weight gain over 2.7 ± 1.3 years, changes in insulin sensitivity were inversely and independently related to changes in mean subcutaneous abdominal adipocyte size and per cent body fat. Conclusion/interpretation. Although enlarged mean subcutaneous abdominal adipocyte size is associated with insulin resistance cross-sectionally, prospectively, both abnormalities are independent and additive predictors of Type II diabetes. [Diabetologia (2000) 43: 1498–1506] Received: 31 July 2000 and in revised form: 6 September 2000     

The impact of a family history of Type II (non-insulin-dependent) diabetes mellitus on the risk of diabetic nephropathy in patients with Type I (insulin-dependent) diabetes mellitus

Aims/hypothesis. There is substantial evidence for a role of genetic factors in the development of diabetic nephropathy. In Pima Indians, a link between susceptibility to diabetic nephropathy and Type II (non-insulin-dependent) diabetes mellitus has been proposed. In this study, our aim was to examine the association between a family history of Type II diabetes and diabetic nephropathy in patients with Type I (insulin-dependent) diabetes mellitus. Methods. In a cross-sectional case-control study, we assessed the prevalence of Type II diabetes in the parents of 137 Type I diabetic patients with diabetic nephropathy (albuminuria > 300 μg/min in two of three overnight urine collections) compared with the parents of 54 Type I diabetic patients without nephropathy (albuminuria < 20 μg/min). Results. Thirty-four (25 %) of the patients with nephropathy compared with five (9 %) of the patients without nephropathy had a parental history of Type II diabetes (p = 0.019). A parental history of Type II diabetes was associated with a three-fold risk [odds ratio 2.95 (95 % confidence interval: 1.03 to 8.40), p = 0.043] of diabetic nephropathy after adjustment for sex, glycaemic control and family history of hypertension. Furthermore, there was an excess of risk factors for development of Type II diabetes (higher fasting plasma glucose concentrations, higher prevalence of hypertension, higher waist-hip ratio and a tendency towards more glucose intolerance) among previously non-diabetic parents of patients with nephropathy. Conclusion/interpretation. Genetic or environmental factors or both related to familial Type II diabetes increase susceptibility to diabetic nephropathy in patients with Type I diabetes. [Diabetologia (1999) 42: 519–526] Received: 30 September 1998 and in final revised form: 28 December 1998     

Pre-diabetic blood pressure predicts urinary albumin excretion after the onset of Type 2 (non-insulin-dependent) diabetes mellitus in Pima Indians

Summary Blood pressure was measured in 490 non-proteinuric Pima Indians from the Gila River Indian Community in Arizona at least 1 year before the diagnosis of Type 2 (non-insulin-dependent) diabetes mellitus. Urine albumin concentration was measured in the same subjects 0–24 years (mean 5 years) after diabetes was diagnosed. Prevalence rates of abnormal albumin excretion (albumin-to-creatinine ratio ≥100 mg/g) after the onset of Type 2 diabetes were 9%, 16%, and 23%, respectively, for the lowest to highest tertiles of pre-diabetic mean blood pressure. When controlled for age, sex, duration of diabetes and pre-diabetic 2-h post-load plasma glucose concentration, higher pre-diabetic mean blood pressure predicted abnormal urinary excretion of albumin after the onset of diabetes. This finding suggests that the higher blood pressure seen in diabetic nephropathy is not entirely a result of the renal disease, but may precede and contribute to it.     

Concordance rate for Type II diabetes mellitus in monozygotic twins: actuarial analysis

Summary To determine the concordance rate for Type II (non-insulin-dependent) diabetes mellitus in monozygotic twin pairs, initially ascertained discordant for diabetes, we carried out a prospective study on 44 non-diabetic subjects, each of whom had a sibling twin with diabetes (21 men, 23 women, median age 55 years, interquartile range 47–65). The subjects were referred as discordant for Type II diabetes. The twin pairs were part of the British Diabetic Twin Study and ascertained between May 1968 and January 1998. These subjects underwent an OGTT at time of referral and periodically thereafter. The mean follow-up was 8 years (range 0–18 years) and data were collected until January 1996. The percentage of twins who developed Type II diabetes was assessed by standard actuarial life-table methods and the pairwise concordance rate, that is the proportion of concordant pairs over the sum of concordant and discordant pairs, was calculated. The observed rates of concordance for Type II diabetes at 1, 5, 10, and 15 years follow-up were 17, 33, 57, and 76 %, respectively. The concordance rate for any abnormality of glucose metabolism (either Type II diabetes or impaired glucose tolerance) at 15 years follow-up was 96 %. The concordance rate for Type II diabetes in monozygotic twins is very high even in twins initially ascertained discordant for diabetes. [Diabetologia (1999) 42: 146–150] Received: 16 March 1998 and in revised form: 26 August 1998     

Class II HLA DNA polymorphisms in Type 1 (insulin-dependent) diabetic patients of North Indian origin

Summary Genetic associations with Type 1 (insulin-dependent) diabetes may be primary or secondary to linkage disequilibrium. Studies of different racial groups should allow these to be distinguished. We have reported that Type 1 diabetes is associated with HLA-DR3 and -DR4 in subjects of North Indian (Punjab) origin and now present the results of a study of HLA class II DNA polymorphisms in this group and in white caucasoid subjects. DR4 in North Indian Type 1 diabetic patients was associated with DQβ and DXα DNA polymorphisms identical to those found in DR4-positive white caucasoid patients. This DQβ/DXα pattern was increased in frequency in North Indian diabetic patients vs control subjects (33.3% vs 8.5%,p<0.001, relative risk=5.12 (95% confidence limits: 1.96–13.4)). A DQβ polymorphism with very low relative risk for Type 1 diabetes in white caucasoid subjects was also markedly reduced in North Indian diabetic patients vs control subjects (2.3% vs 24.7%,p<0.02, relative risk = 0.10 (95% confidence limits: 0.02–0.46)). This pattern was associated with DR2 in white caucasoid subjects, but with DRw6 in North Indians. A DR3-associated DRβ polymorphism was markedly increased in North Indian diabetic patients vs control subjects (90.2% vs 40.7%,p<10⁻⁶, relative risk = 12.1 (95% confidence limits: 4.32–33.9)). The DQ subregion may be a primary site of genetic influence on susceptibility to Type 1 diabetes. Further studies in different racial groups will clarify the HLA associations of Type 1 diabetes.     

C-peptide measurement in the differentiation of Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes mellitus

Summary To determine whether individual subjects with Type 1 (insulin-dependent) diabetes or Type 2 (non-insulin-dependent) diabetes, who are treated with insulin, could be reliably distinguished, C-peptide concentrations and urinary C-peptide excretion were measured in 10 Caucasoids and 10 Pima Indians. All the subjects had developed diabetes before 21 years of age and were receiving insulin treatment. Fasting C-peptide concentrations were significantly higher in the Pima Indians (0.73±0.17 versus 0.02±0.01 nmol/l in Caucasoids; p<0.001), but there were slight overlaps in individual values. Urinary C-peptide excretion, an index of 24-h-insulin excretion, was also higher in the Pima Indian group (27.6±1.85 versus 0.72±0.18 pmol/min in Caucasoids; p<0.001) and there was no overlap in the individual values between the groups. The Pima Indians with early onset diabetes have been previously shown to have Type 2 diabetes, and the Caucasoids with an early onset are most likely to have Type 1 diabetes. These results suggest that distinction between these two major types of diabetes can be made effectively by using C-peptide measurements provided that overt renal disease is absent. This differentiation between insulin-treated patients will be useful for a variety of research applications and possibly in making clinical management decisions.     

Impact of glycaemic control, hypertension and insulin treatment on general and cause-specific mortality: an Italian population-based cohort of Type II (non-insulin-dependent) diabetes mellitus

Summary The aims of this study were to assess the impact of diabetes and associated variables (fasting plasma glucose, blood pressure, antidiabetic treatment, body mass index) on general and cause-specific mortality in an Italian population-based cohort with Type II (non-insulin-dependent) diabetes mellitus, comprising mainly elderly patients. The patients (n = 1967) who had Type II diabetes were identified in 1988 with an 80 % estimated completeness of ascertainment. In 1995, a mortality follow-up (98 % completeness) of the cohort was done amounting to a total of 11 153 person-years. Observed and expected number of deaths were 577 and 428.7, respectively, giving a standardized mortality ratio (SMR) of 1.35 (95 % CI 1.24–1.46). The most common underlying causes of death were malignant neoplasm, ischaemic heart disease and cerebrovascular diseases, which accounted for 18 %, 17.8 % and 17.5 % of deaths, respectively. Cardiovascular disease as a whole (international classification of disease ICD-9 390–459) accounted for 260 of 577 deaths (SMR 1.21, 95 % CI 1.07–1.36). In internal analysis, the most important predictors of general mortality were insulin-treatment (relative risk [RR] 1.72, 95 % CI 1.19–2.49) and a fasting plasma glucose greater than 8.89 mmol/l ([RR] 1.29, 95 % CI 1.04–1.60), whereas the most important predictors of cardiovascular diseases were insulin-treatment and hypertension. In conclusion, this population-based study showed: 1) slight mortality excess of 35 % in Type II diabetes being associated with 2) a 30 % increased mortality in subjects with baseline fasting glucose greater than 8.89 mmol/l and 3) a 40 % increased risk of death from cardiovascular diseases in hypertensive patients. [Diabetologia (1999) 42: 297–301] Received: 27 July 1998 and in final revised form: 17 November 1998     

Incidence of diabetes mellitus in women following impaired glucose tolerance in pregnancy is lower than following impaired glucose tolerance in the non-pregnant state

Summary Impaired glucose tolerance (IGT), which is asymptomatic and requires a glucose tolerance test for detection, is a well-known risk factor for diabetes mellitus. Outside the research setting it is rarely identified in people who lack specific risk factors for diabetes except during pregnancy, at which time screening with an oral glucose challenge is a routine procedure. A 75-g oral glucose tolerance test was performed during the latter part of pregnancy or during a routine epidemiology survey in 15–39-year-old Pima Indian women with no history of abnormal glucose tolerance. Those with IGT by World Health Organization criteria were included in this study. Diabetes incidence in women was compared between those whose IGT was first detected during pregnancy and those who were not pregnant when IGT was first recognized. Seventeen of 73 pregnant women and 114 of 244 non-pregnant women developed diabetes within 10 years. When controlled for plasma glucose concentration, age, body mass index, parity and duration of follow-up, those who were not pregnant were at higher risk of developing diabetes than those who were pregnant (hazard rate ratio = 1.71, 95 % confidence interval = 1.01–2.91). Previous studies had reported that women with IGT during pregnancy are at higher risk of diabetes than women with normal glucose tolerance. This study suggests that women with IGT during pregnancy are at lower risk than non-pregnant women with a similar plasma glucose concentration who, in the clinical setting, are likely to remain unrecognized. [Diabetologia (1996) 39: 1334–1337] Received: 15 February 1996 and in revised form: 8 May 1996     

Increasing incidence of diagnosed type 2 diabetes in Taiwan: analysis of data from a national cohort

Aims/hypothesis Epidemiological evidence shows an increasing prevalence of type 2 diabetes in Taiwan. The aim of this study was to assess the yearly incidence for this country during 1992–1996.Subjects and methods Data obtained by telephone interviews of 93,484 diagnosed diabetic patients enrolled in Taiwan’s National Health Insurance programme formed the basis of this study. A total of 36,153 incident cases of type 2 diabetes (17,097 men and 19,056 women) were identified and incidence rates calculated. The trends of obesity and parental diabetes were also evaluated.Results The overall 5-year incidences for men and women were 187.1 and 218.4 per 100,000 population, respectively. The trends from 1992–1996 were increased for all age groups in men and for most age groups in women. A 2.8-fold increase in incidence was observed for the youngest age group (<35 years), in which the increase in incidence was higher than in the older age groups. Men showed a higher fold increase in incidence than did women (3.5 vs 2.1). Obesity at interview increased from 39.2% in 1992 to 47.6% in 1996 (p<0.001) and was significant for all ages. Parental diabetes showed no yearly change when all patients were analysed together, but there was a trend towards a decrease in the youngest age group (<35 years) and a trend towards an increase in the oldest age groups (≥55 years).Conclusions/interpretation An increasing incidence of diagnosed type 2 diabetes was observed for each sex in most age groups in Taiwan, but was most marked in the youngest age group. A parallel increase in obesity was observed with the increasing incidence of diabetes.     

Incidence of end-stage renal disease in Type 2 (non-insulin-dependent) diabetes mellitus in pima indians

Summary The incidence of end-stage renal disease was determined in the Pima Indians of the Gila River Indian Community in Arizona, a population with a high prevalence of Type 2 (non-insulin-dependent) diabetes mellitus. Between 1975 and 1986, from a study population of 5059 subjects, end-stage renal disease occurred in 80 persons, 76 (95%) of whom had Type 2 diabetes. A review of the cases with end-stage renal disease indicated that among the diabetic subjects only two cases could be attributed to nondiabetic renal disease; all other cases were attributable to diabetic nephropathy. In diabetic Pima Indians the incidence rate of end-stage renal disease did not change during the study period, was similar in men and women, and was not effected by age at diagnosis of diabetes or by attained age, but did increase significantly with hypertension (p<0.05). The incidence of end-stage renal disease attributed to diabetic nephropathy increased from 0 cases/1000 person-years at 0–5 years to 40.8 cases/1000 person-years at 20 years duration of diabetes. In these subjects with Type 2 diabetes, the incidence rate of end-stage renal disease was similar to that in subjects with Type 1 (insulin-dependent) diabetes who were followed at the Joslin Clinic in Boston, Massachusetts when those with similar duration of diabetes were compared.