Social Relationships Among Young Adults with Insulin-dependent Diabetes Mellitus: Ten-year Follow-up of an Onset Cohort

Past cross-sectional studies have suggested that young adults with insulin-dependent (Type I) diabetes mellitus (IDDM) may experience problems in their close peer relationships. For 10 years, we have followed an onset cohort of children and adolescents with IDDM (n = 57) and an age-matched group who were originally recruited after an acute illness, accident, or injury (n = 54). Now aged 19–26 years, these two groups were compared in terms of their friendship patterns, dating and love experiences, and sense of loneliness. All subjects in both groups had at least one friend. However, the IDDM group reported fewer friendships overall. The difference was accounted for by the number of less intimate friends. The two groups had similar frequencies of current romantic partners (IDDM = 63 %; comparison group = 64 %). While dating attitude and dating assertiveness did not differ between groups, some differences were found in terms of experiences of a primary love relationship. IDDM patients experienced less trust and sense of intimate friendship in these love relationships. No differences in loneliness were found. The preponderance of our findings indicate that the two groups had similar patterns and experiences of close peer relationships. Thus, the study does not suggest that IDDM leads to serious problems in forming social relationships for these patients during the transition to young adulthood. On the other hand, the IDDM patients’ lower level of trust and intimacy within love relationships are consistent with other findings from this study suggesting specific areas of lowered self-worth that appear in social relationships. © 1997 by John Wiley & Sons, Ltd.     

The Cost of Insulin-dependent Diabetes Mellitus (IDDM) in England and Wales

This study estimates the direct health and social care costs of insulin-dependent diabetes mellitus (IDDM) in England and Wales in 1992 to be £96 million, or £1021 per person in a population with IDDM estimated at 94 000 individuals. These costs include insulin maintenance, hospitalization, GP and out-patient consultations, renal replacement therapy, and payments to informal carers. Expenditure is concentrated on younger age groups, with one-third of the total expended on those aged 0–24. Around one-half of the total costs can be directly attributed to IDDM, with the remainder associated with a range of complications of the disease. The single largest area of service expenditure is renal replacement therapy. The cost estimates are most sensitive to incidence rates of IDDM, numbers on dialysis and average duration of dialysis. A further £113 million pounds may be lost each year due to premature deaths resulting in lost productive contributions to the economy. The direct and indirect costs of IDDM are therefore significant. The cost of illness framework presented here should facilitate the economic evaluation of new and existing treatment regimens, which may improve value for money by reducing costs and/or increasing the quality or quantity of life for people with IDDM.     

HLA and Glutamic Acid Decarboxylase in Human Insulin-dependent Diabetes Mellitus

Insulin-dependent diabetes mellitus (IDDM) is linked to HLA factors on human chromosome 6 and strongly associated with the presence of autoantibodies against the glutamic acid decarboxylase isoform GAD65. These autoantibodies, GAD65Ab are detected both before and at the time of clinical diagnosis. Molecular sequencing of HLA alleles and PCR-based genotyping have improved our understanding of the linkage between HLA and IDDM. At the same time, the molecular cloning of human islet GAD65 and the development of precise and reproducible GAD65Ab assays with recombinant human GAD65 has given new insights to the problem of to what extent HLA control the development of a GAD65 immune response or to the development of IDDM. Recent data are briefly reviewed. In new onset IDDM patients GAD65Ab were associated with the DQ2/8 or DQ2/X genotype. However, in patients with an older age at onset the association was particularly pronounced with the DQ2/8 genotype. The DQ5/8 genotype was significantly decreased among GAD65Ab positive patients. Certain DQ genotypes, therefore, seem permissive for the formation of GAD65Ab in IDDM. Studies of the general population is needed to determine if the DQ2, 8 or both alleles predispose to GAD65 autoreactivity. This is important since other factors may control the development of IDDM in only a fraction of GAD65 antibody positive individuals detected following a screening of the general population.     

Short-term Mortality in Childhood Onset Insulin-dependent Diabetes Mellitus: a High Frequency of Unexpected Deaths in Bed

Mortality and the causes of death have been studied in a population-based cohort of 4919 childhood onset IDDM cases. Enrolment began in 1977 and at the time of study there had been a maximum duration of disease of 13.5 years, with a total of 33 721 person years at risk. Survival status was ascertained by linkage to the Swedish Cause-of-Death register. Death certificates, autopsy protocols, and hospital records were scrutinized for classification of causes of deaths. Twenty males and 13 females with IDDM died before the age of 28.5 years. This corresponds to a Standardized Mortality Rate for age of 262% (95% confidence limits, 172–400) for the boys and 384% (95% confidence limits, 232–635) for girls. Seven patients died of ketoacidosis, four at onset of diabetes. Nine cases were found ‘dead in bed’, having been seen apparently healthy 1–2 days before death. One of these cases had signs of cerebral haemorrhages at autopsy and another one had signs of bite marks in the mouth, but otherwise all autopsies were normal and no evidence of alcohol or other intoxication was found. In a well-educated population with good access to inexpensive diabetes care, there is still a two- to threefold excess mortality among young onset insulin-dependent diabetic individuals including a high frequency of unexplained deaths in bed.     

Newly Diagnosed,Insulin-dependent Diabetes Mellitus in Elderly Patients

Over a two-year period 398 out of 1776 new referrals to a diabetic clinic were newly diagnosed diabetic patients aged 65 years and over. Initial treatment of this group was diet—122 (31%), diet plus oral hypoglycaemic agents—232 (58%) and diet plus insulin—41 (10%). Sixteen (39%) of the group treated initially with insulin died within 3.5 years of diagnosis compared with 21% of the 345 patients treated with diet ±oral hypoglycaemic agents who were followed for this time. Twenty-five patients treated initially with insulin survive but 8 have stopped insulin and are treated with diet ±oral hypoglycaemic agents, and a further 5 had a period of 6–24 months on oral therapy. Twelve patients have been treated with insulin continuously but of these only 3 are clearly insulin-dependent. These data suggest that true dependence on insulin is uncommon in patients aged 65 years or over at diagnosis.     

Characterization of the Insulin-antagonistic Effect of Growth Hormone in Insulin-dependent Diabetes Mellitus

To characterize its insulin-antagonistic effect, growth hormone (GH) was infused at variable rates (24, 12 or 6 ***mU kg^?1 min^?1) for 1 h in 7 IDDM patients. Saline infusion was used as control (C) and all patients participated in all studies. The effect of insulin was measured with the euglycaemic clamp technique for 6 h combined with d–(3–³H)–glucose to evaluate glucose turnover. The insulin levels during the clamps were similar in all studies (23 ± 3 ***mU I^?1). The infusions produced peak GH levels of (24 rate = 24) 157 ± 11, (12 rate = 12) 76 ± 7, and (6 rate = 6) 45 ± 8 ***mU 1^?1 (mean ± SEM). The insulin-antagonistic effect of GH on glucose uptake was seen after 2 h and was at a maximum 4 to 5 h after the start of the GH infusion (difference in glucose infusion rate between C and 24 was 1.7 ± 0.4 mg kg^?1 min^?1p < 0.01). The resistance was due to a less pronounced effect of insulin to both inhibit rate of appearance and to stimulate rate of disappearance. Infusion of GH at 12 mU kg^?1 min^?1 induced a less pronounced insulin resistance both with regards to maximal effect (glucose infusion rate C - GH 1.4 ± 0.5 mg kg^?1 min^?1p < 0.05) and duration (3 h). At 6 ***mU kg^?1 min^?1a clear GH-induced insulin-antagonistic effect was only seen during the third hour of the clamp (glucose infusion rate C-GH 1.3 ± 0.5 mg kg^?1 min^?1p < 0.05). GH infusion impaired the effect of insulin to lower both the levels of free fatty acids (NEFA) and glycerol between 2 and 5 h after the start of the infusion (NEFA, C:110 ± 29, 24:303 ± 95, p < 0.05: glycerol, C:32 ± 4, 24:50 ± 7 μmol I^?1p < 0.05). The present study therefore demonstrates that the insulin-antagonistic effect of GH in IDDM is related to the plasma levels both with regard to duration and response. The results also indicate that GH impairs the effect of insulin on lipolysis in IDDM after physiological peaks.     

Serum Sialic Acid and the Long-term Complications of Insulin-dependent Diabetes Mellitus

Elevated serum sialic acid (SSA) predicts cardiovascular disease in the non-diabetic population and is also associated with the presence of microalbuminuria and clinical proteinuria in patients with insulin-dependent diabetes (IDDM). We have studied 121 patients with IDDM of long duration (mean duration 25.2 years) to investigate the relationship of SSA concentrations to the presence of retinopathy, nephropathy, and neuropathy. SSA levels were elevated in patients with retinopathy (0.578 ± 0.161 g l⁻¹, n = 98) when compared with those without retinopathy (0.468 ± 0.145 g l⁻¹, n = 23, p = 0.002). Patients with nephropathy (urinary albumin:creatinine ratio of > 3 mg mmol⁻¹ in all of three early morning specimens of urine) also had raised SSA levels (0.625 ± 0.169 g l⁻¹, n = 30) compared with those without nephropathy (0.533 ± 0.160 g l⁻¹, n = 91, p = 0.006). There was a significant correlation of SSA with urinary albumin:creatinine ratio (correlation coefficient 0.33, p < 0.001). SSA levels were not related to the presence or absence of neuropathy (0.567 ± 0.181 g l⁻¹, n = 28, vs 0.533 ± 0.160 g l⁻¹, n = 93, p = 0.92, respectively). In conclusion, retinopathy and nephropathy but not neuropathy are associated with increased SSA levels in patients with IDDM. The significance of this is not yet clear but it is possible that sialic acid is involved in the pathophysiology of microvascular disease in IDDM.     

A Longitudinal Study of Biomedical and Psychosocial Predictors of Multiple Hospitalizations Among Young People with Insulin-dependent Diabetes Mellitus

The aim of the present study was to estimate the cumulative probability of multiple diabetes-related hospitalizations and identify associated risk factors in a sample of 92 school-age children, newly diagnosed with insulin-dependent (Type 1) diabetes mellitus, who were followed longitudinally for up to 14 years (mean: 9 years). ‘Multiple hospitalizations’ as a variable was defined as three or more admissions. Altogether 26 young patients (28%) had multiple admissions (with a total of 158 hospitalizations), yielding an estimated cumulative probability for this outcome of 0.33 by 10 years after onset of diabetes. Multivariate longitudinal analyses revealed that at any given point in time, four variables significantly increased the risk of multiple admissions: higher levels of glycosylated haemoglobin reflecting poorer metabolic control, higher levels of externalizing symptoms reflecting greater behaviour problems, younger age at diagnosis, and lower socio-economic status. According to the results of post hoc analyses, however, the aforementioned risk factors do not appear to be specific to multiple hospitalizations, and can serve to identify groups that are generally vulnerable to readmissions.     

Response of Apolipoprotein AIV and Lipoproteins to Glycaemic Control in Young People with Insulin-dependent Diabetes Mellitus

Young people with insulin-dependent diabetes mellitus (IDDM) (n = 104, 7 to 19 years old) were classified into groups of good (I), fair (II), and poor (III) diabetic control and compared to 22 healthy controls of same origin and age range. Triglycerides (TG) were significantly elevated with respect to controls only in group III, and total cholesterol was increased by over 40 % (p < 0.01) mainly due to low density lipoprotein-cholesterol (LDL-C). Apolipoprotein B (apo B) was over 40 % higher in groups II and III. TG, LDL-C, and apo B concentrations all positively correlated with HbA_1c levels. Neither HDL-C nor apolipoprotein AI (apo AI) were affected by glycaemic control, but phospholipids were increased in all three subgroups of IDDM subjects (p < 0.001). Over the course of 6 months’ treatment, TG, apo B, and LDL-C varied in parallel with HbA_1c, confirming a tight association with the quality of glycaemic control. Apolipoprotein AIV (apo AIV) was higher in all groups and closely related to glycaemic control (r = +0.43, p < 0.001), independent of TG or HDL. The specific and sensitive response of apo AIV to insulin deficiency suggests a direct effect at the level of intestinal synthesis. © 1997 by John Wiley & Sons, Ltd.     

Successful Immune Response to a Recombinant Hepatitis B Vaccine in Young Patients with Insulin-dependent Diabetes Mellitus

The study aimed to evaluate the immune response to a recombinant hepatitis B vaccine in young patients with insulin-dependent diabetes mellitus (IDDM), in view of reports of reduced efficacy in adults with IDDM. Sixty-five young people with IDDM, age 4.5 to 27.5 and diabetes duration 0.3 to 19 years and 174 age- and sex-matched healthy subjects were injected with a recombinant hepatitis B vaccine at 0, 1, and 6 months intramuscularly in the deltoid region. Three (4.6 %) IDDM patients and 2 (1.1 %) controls were non-responders (HBsAb titre, <2 IU l⁻¹) and 1 control was a low responder (HBsAb titre = 10 IU l⁻¹). Among the 3 non-responder IDDM subjects, 2 had other autoimmune disease. Median HBsAb titre was similar in responding patients (120 IU l⁻¹) and controls (125 IU l⁻¹). There were no significant correlations between antibody titre and age, diabetes duration, HbA_1c or insulin requirement. No association was found between HBsAb titre and any HLA genotype or the presence of microangiopathy. IDDM does not adversely affect the immune response to a recombinant hepatitis B vaccine in children, adolescents, and young adults, who can thus expect to benefit from its use in situations of risk of contracting hepatitis.     

The Nephrotic Syndrome at Presentation of Insulin-dependent Diabetes Mellitus; Cause or Coincidence?

Two young women developed the nephrotic syndrome within 2 weeks of presenting with diabetes and starting insulin. One had a renal biopsy which showed changes consistent with 'minimal change nephrotic syndrome' on electron microscopy but no evidence of diabetic glomerulosclerosis. Neither patient received steroids; in one the oedema resolved spontaneously but the other required diuretics. This patient also had severe IgA-deficiency probably associated with epilepsy and/or phenytoin therapy and unrelated to the pathogenesis of the nephrotic syndrome. The nephrotic syndrome may rarely present coincidentally with, or soon after, insulin-dependent diabetes mellitus (IDDM). It must be distinguished from 'insulin oedema' and classical diabetic nephropathy which occurs later in the course of IDDM. All reported cases have either remitted spontaneously or responded to steroids.     

The Effect of an Angiotensin Converting Enzyme Inhibitor on Skin Microvascular Hyperaemia in Microalbuminuric Insulin-dependent Diabetes Mellitus

Patients with longstanding insulin-dependent (Type 1) diabetes mellitus (IDDM) are reported to have microvascular complications in most capillary beds. The microvascular hyperaemia of the skin in normoalbuminuric and microalbuminuric IDDM patients and healthy volunteers was measured with laser Doppler flowmetry. The effect of 3 and 9 months of treatment with captopril, an angiotensin converting enzyme inhibitor, on hyperaemia in the microalbuminuric patients was studied. Mean (±SD) pretreatment duration of skin postocclusive reactive hyperaemia was longer in microalbuminuric than in both normoalbuminuric patients and healthy volunteers (118.2 ± 34.4 vs 57.8 ± 16.0 vs 63.3 ± 18.3 sec, respectively, p < 0.00001). After 3 and 9 months of captopril treatment the prolonged hyperaemia was shortened to 78.6 ± 45.6 s (p < 0.01) and 62.3 ± 55.6 s (p < 0.03), respectively. Urinary albumin excretion decreased from 63.9 ± 43.5 to 33.4 ± 28.1 mg 24 h⁻¹ at 3 months treatment (p < 0.002) and 43.1 ± 38.5 mg 24 h⁻¹ at the end of the study period (p <0.02). A positive correlation between changes in urinary albumin excretion and the shortening of the skin postocculsive reactive hyperaemia was found. Blood pressure remained in the same range throughout. These results show that captopril affects skin blood flow, independent of its hypotensive effect. This action may reflect the influence of angiotensin converting enzyme inhibitor on vascular beds other than those of the kidneys. © 1997 by John Wiley & Sons, Ltd.     

成人晚发1型糖尿病相关抗体检测意义

将３２５例成人晚发１型糖尿病患者分成胰岛素（ＬＮＳ）分泌缺乏及非ＩＮＳ分泌缺乏两组,用间接酶联免疫吸附（ＥＬＩＳＡ）法测定其县岛细胞坑体（ＩＣＡ）、胰岛素抗体（ＩＡＡ）及谷氨酸脱羧酶抗体（ＧＡＤ－Ａｂ）,比较其相关性。结果两组ＩＣＡ、ＧＡＤ、Ａｂ阳性率、酮症发生率及体重指数有显著性差异。证明ＩＣＡ、ＧＡＤ－Ａｂ可作为成人晚发１型糖尿病的早期筛选指标。     

Randomized Trial Comparing Nicotinamide and Nicotinamide Plus Cyclosporin in Recent Onset Insulin-dependent Diabetes (IMDIAB 1)

A 1-year open randomized controlled multicentre trial was carried out on 90 patients with recent onset (< 4 weeks) insulin-dependent diabetes (IDDM) to compare the effect of nicotinamide (NCT) with the combination NCT and low dose cyclosporin (CyA) on clinical remission and optimization of metabolic control during the first year from diagnosis. Three groups of patients were randomly assigned to receive for 12 months either NCT 25 mg kg^?1 day^?1 (n = 30) or NCT 25 mg kg^?1 day^?1 + CyA 5 mg kg^?1 day^?1 (n = 30), the latter adjusted to maintain 12 whole blood trough levels of 83 nmol l^?1; a third group of patients (n = 30) receiving insulin only acted as a control group for spontaneous remission and metabolic control. Clinical remission (i.e. suspension of insulin therapy with normal metabolic parameters for more than 2 weeks according to the International Diabetes Immunotherapy Group) was achieved at 3 months in 6/30 NCT treated patients and in 1/30 NCT + CyA treated patient (p = 0.05); no remission was observed in control patients. At 6 months the number of patients achieving remission in each group was 4/29, 3/27, and 1/29, respectively (p = NS). One year after diagnosis 4/27 NCT treated, 2/25 NCT+ CyA treated but 0/28 of the control patients were in remission (NCT vs control p = 0.05). Clinical remission lasted longer (7 ± 3 SD months) in NCT treated patients than in NCT+ CyA treated or control patients (p < 0.02). In patients who did not show clinical remission, there were no significant differences in the integrated measures of metabolic control (HbA₁ and C peptide) between the two groups; however, NCT+ CyA treated patients only required significantly less insulin at 12 months compared to control patients (p < 0.02). Side-effects were not observed in patients receiving NCT and were minimal in those treated with the combination of NCT+ CyA. We conclude that nicotinamide alone is a safe and effective adjunct to insulin in the early phase of IDDM to increase the rate of clinical remission and to improve integrated parameters of metabolic control.     

糖尿病病人患冠心病心肌代谢临床研究进展

通过研究糖尿病病人以及糖尿病病人冠心病的心肌能量代谢,揭示了脂肪酸氧化增加和葡萄糖氧化降低是糖尿病病人冠心病的心肌能量代谢障碍的主要原因,抑制脂肪酸氧化,刺激或增加葡萄糖氧化,可以优化糖尿病病人冠心病的心肌代谢.     

Coeliac autoimmunity in type I diabetes mellitus

Background and study aimsCoeliac autoimmunity (CA) has a known association with type 1 diabetes mellitus (T1DM) for which screening is routinely recommended but less frequently followed. The impact of CA in T1DM has been variably reported. The aims of this study are as follows: (1) to study the prevalence of CA in patients with T1DM and (2) to study the impact of CA not only on nutritional parameters but also on glycaemic control, endocrine axes and bone health.Patients and methodsEighty-six consecutive patients with T1DM were screened for CA using immunoglobulin A (IgA) tissue transglutaminase as a marker (TTG; IgG anti-gliadin in IgA-deficient case). CA positive (CA+) cases were compared with age-matched and sex-matched CA negative (CA−) T1DM cases for anthropometry, glycaemic control (assessed by glycated haemoglobin (HbA1c) and hypoglycaemic/hyperglycaemic episodes), endocrine (thyroid function, cortisol, growth hormone (GH) axis, gonadal axes), haematological (haemoglobin, iron profile and vitamin B₁₂ status) and calcium metabolism parameters and bone densitometry (by dual-energy X-ray absorptiometry (DXA)). Consenting patients with CA also underwent upper gastrointestinal (GI) endoscopy with duodenal biopsy.ResultsOut of 86 patients, 11 (12.75%) screened positive for CA (seven patients underwent duodenal biopsies which were suggestive of Marsh grade III(2), II(3) and I(2) disease). The CA+ T1DM patients were comparable with CA− T1DM in terms of anthropometry. CA+ patients had higher HbA1c (10.7 ± 1.8 vs. 8.4 ± 1.0 (93 ± 19 vs. 68 ± 11 mmol/mol); p < 0.01), more hypoglycaemic episodes (five vs. two; p < 0.05), higher prevalence of iron and vitamin B₁₂ deficiency, lower insulin-like growth factor-1 (IGF-1) levels and lower bone mineral density (BMD) z-score at total body (−1.91 ± 1.05 vs. −0.63 ± 0.73; p < 0.05) and lumbar spine (−1.69 ± 0.92 vs. −0.36 ± 0.93; p < 0.05). The incidence of fractures in the past 3 years was also more in CA+ patients than in CA− patients (four vs. one; p < 0.05).ConclusionCA has an important autoimmune association with T1DM. The concomitant presence of CA adversely affects stature, bone health, glycaemic control and iron and B₁₂ levels in T1DM. IgA sufficiency should be ensured before using an IgA-based screening test for CA.     

Studies of Insulin Resistance Following Hypoglycemia in Insulin-dependent Diabetes Mellitus

ABSTRACT Insulin resistance was assessed after a hypoglycemia induced by insulin (1.5 mU×kg^-1 ×min^-1) between 7 and 8 a.m. in 10 well-insulinized patients with insulin-dependent diabetes mellitus (IDDM). Blood glucose levels during a somatostatin (100 μg×h^-1)-insulin (0.4 mU×kg^-1×min^-1)-glucose (4.5 mg×kg^-1)-infusion test (SIGIT) performed between 11 a.m. and 3 p.m. served as an indicator of total body insulin resistance. Plasma epinephrine, growth hormone, and Cortisol increased in response to hypoglycemia, while blunted responses of glucagon were simultaneously registered. At the start of the subsequent SIGIT, blood glucose and plasma-free insulin concentrations were similar to those obtained in the control study without preceding hypoglycemia, and at this point all counter-regulatory hormones had returned to basal. During the SIGIT close to identical levels of plasma-free insulin and counter-regulatory hormones were registered, despite which a significant hyperglycemia was seen 2 hours after the start of the SIGIT when preceded by hypoglycemia. In a separate study, the SIGIT was shown to have a good reproducibility in IDDM patients. We conclude that hypoglycemia evokes a state of insulin resistance for several hours, as demonstrated by elevated blood glucose levels during a somatostatin-insulin-glucose-infusion test.     

Prader-Willi Syndrome with Slowly Progressive Insulin-dependent Diabetes Mellitus

We report the case of a 52-year-old woman with Prader-Willi syndrome (PWS) and diabetes. Her diabetes was managed with sulfonylurea followed by premixed insulin; however, her glycemic control gradually worsened and became unstable. Her urine and blood C-peptide levels were undetectable. She tested positive for anti-GAD antibodies, and had a high-risk genotype - DRB1*09:01-DQB1*03:03 - for slowly progressive insulin-dependent diabetes mellitus (SPIDDM) in the HLA-DR/DQ region, confirming the diagnosis of SPIDDM. Dysglycemia in PWS is thought to be attributable to hyperphagia and obesity. However, the possibility of SPIDDM might be considered if the insulin secretory capacity is almost lost in patients with PWS.     

Does the Prepubertal Duration of Diabetes Influence the Onset of Microvascular Complications?

This study investigated the relationship between the development of diabetic retinopathy and pubertal status at onset of diabetes in 521 Type 1 diabetic patients diagnosed between 1950 and 1985. Pubertal status was based on age at onset (girls ≧ 11 years and boys ≧ 12 years). Retinopathy (all forms) developed in 112 patients (21.5%; 65 background and 47 proliferative retinopathy). For subjects diagnosed in either the prepubertal or postpuberal period, a similar proportion survived without developing retinopathy for any given duration of diabetes (X² = 0.3822, p = 0.54). However, if only the postpubertal duration of diabetes is considered, then the proportion of patients surviving without retinopathy was significantly less for those diagnosed in the prepubertal period (X² = 14.2, p = 0.002). This study suggests that the prepubertal duration of diabetes is an important phase and that the years prior to puberty do contribute to the risk of developing microvascular injury.