Plasma homocysteine concentrations in patients with type 1 diabetes

OBJECTIVE: To determine the plasma concentration of total homocysteine (tHcy), a recognized risk factor for vascular disease, in patients with type 1 diabetes and to examine the relationships with age, sex, duration of diabetes, microvascular complications and neuropathy, and folic acid concentration. RESEARCH DESIGN AND METHODS: Plasma tHcy and folic acid concentrations were measured in a randomly selected cohort of type 1 diabetic patients (n = 119), well characterized as regards microvascular complications, and in a matched control group (n = 51). RESULTS: Plasma tHcy was higher in male than in female control subjects (geometric mean [95% CI]: 9.3 [8.0-10.9] vs. 6.1 [5.2-7.2] micromol/l, P < 0.001), as previously described, but there was no sex difference in diabetic patients. Plasma tHcy significantly correlated with age in patients (r = 0.348, P < 0.01) but not in control subjects (r = 0.007, P = 0.96). Male patients without microvascular complications had lower plasma tHcy concentrations than did male control subjects (6.2 [5.1-7.5] vs. 9.3 [8.0-10.9] micromol/l, P < 0.001), but values in female patients without complications were similar to those of female control subjects. Plasma folic acid concentration was higher in diabetic patients than in control subjects. The expected negative association between plasma tHcy and folic acid was stronger in control subjects than in patients. CONCLUSIONS: Subnormal tHcy concentrations in male patients, the absence of a sex difference, and the positive association with age indicate that homocysteine metabolism differs between type 1 diabetic patients and control subjects. Homocysteine is unlikely to be of pathogenic significance in patients, particularly male subjects, with early microvascular disease and/or neuropathy.     

Daily energy metabolism in patients with type 1 diabetes mellitus

The availability of markers for the 17p11.2 region has enabled the diagnosis of Smith-Magenis syndrome (SMS) by fluorescence in situ hybridization (FISH). SMS is typically associated with a discernible deletion of band 17p11.2 upon cytogenetic analysis at a resolution of 400-550 bands. We present a case that illustrates the importance of using FISH to confirm a cytogenetic diagnosis of del(17)(p11.2). Four independent cytogenetic analyses were performed with different conclusions. Results of low resolution analyses of amniocytes and peripheral blood lymphocytes were apparently normal, while high resolution analyses of peripheral blood samples in two laboratories indicated mosaicism for del(17)(p11.2). FISH clearly demonstrated a 17p deletion on one chromosome of all peripheral blood cells analyzed and ruled out mosaicism unambiguously. The deletion was undetectable by flow cytometric quantitation of chromosomal DNA content, suggesting that it is less than 2 Mb. We conclude that FISH should be used to detect the SMS deletion when routine chromosome analysis fails to detect it and to verify mosaicism.     

Acute renal failure in patients with type 1 diabetes mellitus

Acute renal failure (ARF) is a serious condition which still carries a mortality of around 50%. People with diabetes may be at increased risk of developing ARF, either as a complication of diabetic ketoacidosis or hyperosmolar coma, increased incidence of cardiovascular disease, or due to increased susceptibility of the kidney to adverse effects in the presence of underlying diabetic renal disease. During the period 1956-1992, 1,661 cases of ARF have been treated at Leeds General Infirmary. Of these, we have identified 26 patients also having type 1 diabetes. ARF due to diabetic ketoacidosis is surprisingly uncommon (14 cases out of 23 patients whose notes were reviewed). All cases of ARF complicating ketoacidosis in the last decade have been associated with particularly severe illness requiring intensive care unit support, rather than otherwise 'uncomplicated' ketoacidosis. We discuss the conditions that may result in ARF in patients with diabetes and the particular difficulties that may be encountered in management.     

Validation of a diabetes-specific quality-of-life scale for patients with type 1 diabetes

OBJECTIVE: To validate a diabetes-specific quality-of-life scale and to assess its psychometric properties in a large sample of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: To assess the quality of diabetes care in a population-based study, a representative sample of 684 patients with type 1 diabetes was examined. A total of 657 patients (42% female; mean age 36 years; mean diabetes duration 18 years) completed the diabetes-specific quality-of-life scale (DSQOLS), which comprised 64 items on individual treatment goals (10 items), satisfaction with treatment success (10 items), and diabetes-related distress (44 items). Statistical examinations covered factor analysis, internal consistency of subscales, and construct and discriminant validity. RESULTS: Factor analysis of the 44 items on diabetes-specific burdens revealed six reliable components (Cronbach's alpha): social relations (0.88), physical complaints (0.84), worries about future (0.84), leisure time flexibility (0.85), diet restrictions (0.71), and daily hassles (0.70). All six subscales were significantly correlated with a validated well-being scale (r = -0.35 to -0.53, P < 0.001) and treatment satisfaction (r = 0.28 to 0.43, P < 0.001). Physical complaints (r = 0.24) and worries about future (r = 0.17) showed the highest correlations with HbA1c (P < 0.001). A flexible insulin therapy, a liberalized diet, the absence of late complications, and a higher social status were significantly associated with more favorable scores in different domains. CONCLUSIONS: The DSQOLS is a reliable and valid measure of diabetes-specific quality of life. The scale is able to distinguish between patients with different treatment and dietary regimens and to detect social inequities. Use of the DSQOLS for assessment of individual treatment goals as defined by the patients may be helpful to identify motivational deficits and to tailor individual treatment strategies.     

Reduced beta-adrenergic sensitivity in patients with type 1 diabetes and hypoglycemia unawareness

OBJECTIVE: We tested the hypothesis that impaired tissue sensitivity to catecholamines contributes to hypoglycemia unawareness in subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 21 subjects with type 1 diabetes underwent a standardized insulin infusion protocol to produce a stepwise decrease in plasma glucose to 45-min plateaus of 4.3, 3.6, 3.0, and 2.3 mmol/l. Glycemic thresholds, maximum responses for adrenergic and neuroglycopenic symptoms, and counterregulatory hormones were determined. Patients were classified as hypoglycemia unaware if the initiation of adrenergic symptoms occurred at a plasma glucose level 2 SD below that of nondiabetic volunteers. beta-Adrenergic sensitivity was measured as the dose of isoproterenol required to produce an increment in heart rate of 25 beats per minute above baseline (I25) in resting subjects. RESULTS: Subjects with type 1 diabetes and hypoglycemia unawareness experienced the onset of adrenergic symptoms at a lower plasma glucose level than did those with awareness (2.5+/-0.1 vs. 3.7+/-0.1 mmol/l, P < 0.001), whereas neuroglycopenic symptoms occurred at similar glucose levels (2.7+/-0.2 vs. 2.8+/- 0.1 mmol/l). The plasma glucose levels for counterregulatory hormone secretion (epinephrine 2.9+/-0.2 vs. 4.1+/-0.2 mmol/l; norepinephrine 2.7+/-0.1 vs. 3.2+/-0.2 mmol/l; cortisol 2.5+/-0.2 vs. 3.3+/-0.2 mmol/l, P < 0.01) were also lower in subjects with unawareness. The maximal epinephrine (1,954+/-486 vs. 5,332+/- 1,059 pmol/l, P < 0.01), norepinephrine (0.73 +/- 0.14 vs. 1.47+/-0.21 nmol/l, P = 0.04), and cortisol (276+/-110 vs. 579+/-83 nmol/l, P < 0.01) responses were reduced in the unaware group. I25 was greater in unaware subjects than in subjects without unawareness (1.5+/-0.3 vs. 0.8+/-0.2 microg), where I25 was not different from that of controls (0.8 +/-0.2 microg). CONCLUSIONS: We conclude that subjects with type 1 diabetes and hypoglycemia unawareness have reduced beta-adrenergic sensitivity, which may contribute to their impaired adrenergic warning symptoms during hypoglycemia.     

Transmission of human T-cell leukemia virus type 1 to mice

Human T-cell leukemia virus type 1 (HTLV-1) is associated with adult T-cell leukemia/lymphoma, HTLV-1-associated myelopathy/tropical spastic paraparesis, and other diseases. For prevention of the transmission of HTLV-1 and manifestation of these diseases, a small-animal model, especially a mouse model, would be useful. We injected HTLV-1-producing T cells (MT-2) intraperitoneally into neonatal C3H/HeJ mice. While the antibody against HTLV-1 antigens was not detectable in C3H/HeJ mice, HTLV-1 provirus was frequently detected in the spleen, lymph nodes, and thymus by PCR. HTLV-1 provirus was present at the level of 0 to 30 molecules in 10(5) spleen cells at the age of 15 weeks. In addition, a 59-bp flanking sequence of the HTLV-1 integration site was amplified from the spleen DNA by linker-mediated PCR and was confirmed to be derived from the mouse genome. HTLV-1 provirus was found in the T-cell fraction of the mouse spleen. These results indicate that mice can be infected by HTLV-1 and could serve as an animal model for the study of HTLV-1 infection and its pathogenesis in vivo.     

Management of hospitalized patients with type 2 diabetes mellitus

Subopitmal glycemic control in hospitalized patients with type 2 (non-insulin-dependent) diabetes mellitus can have adverse consequences, including increased neurologic ischemia, delayed wound healing and an increased infection rate. Poor glycemic control can also affect the outcome of the primary illness. If possible, hospitalized diabetic patients should continue their previous antihyperglycemic treatment regimen. Decreased physical activity and the stress of illness often lead to hyperglycemia in hospitalized patients with type 2 diabetes. When indicated, insulin is given either as a supplement to usual therapy or as a temporary substitute. The overall benefit of the traditional sliding-scale insulin regimen has been questioned. Insulin supplementation given according to an algorithm may be a logical alternative. Any antihyperglycemic regimen should be administered and monitored in a manner coincident with the intake of food or other sources of calories. Factors that can alter glycemic control acutely, including specific medical conditions and medications, should be identified and anticipated.     

Obesity among offspring of women with type 1 diabetes

OBJECTIVE: To determine subsequent growth and body composition of children born to women with type 1 diabetes compared with controls. DESIGN: Prospective cohort study. SETTING: Follow-up of offspring born to women with type 1 diabetes and controls from an earlier study of diabetes and lactation. SUBJECTS: Seventeen nondiabetic offspring of women with type 1 diabetes and 18 offspring of control women (age range 5.9 to 9.0 years). OUTCOME MEASURES: Anthropometric measures at follow-up included height, weight, triceps and subscapular skinfold thickness. Information on usual nutrient intakes and physical activity patterns was elicited through questionnaires. Body composition was determined from skinfold thickness measures and bioelectrical impedance analysis. A child was identified as obese if he or she met at least 2 of the following 4 criteria for obesity: (1) weight-for-height equal to or greater than 120% of the National Center for Health Statistics (NCHS) reference median plus triceps skinfold greater than the 85th percentile; (2) body mass index (BMI) greater than the 95th percentile for age and sex; (3) percent body fat (from impedance measures) equal to or greater than 25 for boys and 30 for girls; or (4) percent body fat (from sum of skinfold measures) equal to or greater than 25 for boys and 30 for girls. RESULTS: There were 7 obese children in the type 1 diabetes group and none in the control group (p = 0.007). Obese children did not differ from nonobese children in birth weight, body fat patterning, nutrient intake, physical activity patterns, maternal pregravid weight or blood glucose control during the last trimester of pregnancy. Mothers of obese children, however, had fewer years of education and gained more weight during pregnancy compared with mothers of nonobese children in the type 1 diabetes group (p < 0.05). CONCLUSION: Obesity during childhood is a significant problem among nondiabetic children of women with type 1 diabetes. The association of childhood obesity with lower maternal education and excessive pregnancy weight gain warrants further investigation.     

Impaired vibration perception threshold and long-term mean HbA1c in patients with type 1 diabetes mellitus

The impact of long-term glycaemic control, assessed as HbA1c for 5 years or more, on vibration perception threshold (VPT) in Type 1 (insulin-dependent) diabetes was investigated. Patients with diabetes onset before 31 years of age and with a diabetes duration of < 26 years were included. HbA1c was on average monitored over 9.2 years with 32 measurements. VPT was measured with biothesiometry on the big toes, and compared to non-diabetic reference values standardized for age and height. The biothesiometry readings in the group of 207 patients were elevated. The median z score (z-transformation of In (VPT)) was 1.4 in the diabetic population. Patients with HbA1c > 7.8% (highest quartile) had a relative risk of 9.2 (95% CI 3.5 < RR < 24.0) to be among the 10% with the highest z score for VPT, compared to patients with HbA1c < 7.8%. Stepwise forward linear regression analysis with the log normal of the VPT as dependent variable included age, HbA1c, height, body mass index, macroalbuminuria, and hypertension (> 140/90 mmHg or antihypertensive treatment) as explaining variables. In conclusion, impaired VPT was strongly associated with high long-term HbA1c.     

Intensive treatment of type 1 diabetes

There have been amazing advances for the treatment of type 1 diabetes. As clinicians proceed into the twenty-first century, it is appropriate to reflect both about accomplishments and about the prospects of improved therapeutic options. Regarding the former, perhaps no advance can be compared to the discovery of insulin. Since then, the improvements in therapy have appeared to be too slow for physicians, patients, and their families. In actuality, over the past 20 years, the pace for the development of new tools for the treatment of this once fatal disease has been remarkable. The treatment of type 1 diabetes has evolved with advances in the treatment of microvascular, neuropathic, and macrovascular complications. The future is even more promising, with the possibility of even preventing the disease before the development of hyperglycemia. The challenge for the present is teaching all individuals involved with the management of patients with type 1 diabetes to manage the condition as effectively as possible.     

Long-term administration of theophylline and glucose recovery after hypoglycaemia in patients with type 1 diabetes mellitus

The methylxanthine theophylline increases intrahepatic c-AMP and c-AMP mediates the hepatic glucose response to adrenaline and glucagon. Intravenous theophylline increases glucose recovery during acute insulin-induced hypoglycaemia and caffeine increases hypoglycaemia awareness and glucoregulatory hormone secretion. In this study we tested the hypothesis that long-term administration of theophylline might augment glucose recovery after insulin-induced hypoglycaemia. Eleven healthy subjects and 8 patients with Type 1 diabetes mellitus were made hypoglycaemic by 60 min insulin infusion (40 mU m(-2)) after 2 weeks' oral therapy with Euphyllin Retard (theophylline) or placebo. Plasma glucose nadir was 2.54 (2.31-2.77) mmol l(-1) after Euphyllin Retard and 2.27 (2.05-2.48) mmol l(-1) after placebo (mean difference 0.26 (0.05-0.58) mmol l(-1), p = 0.09) for healthy control subjects and 2.56 (2.07-3.04) mmol l(-1) and 2.19 (1.37-2.65) mmol l(-1) (mean difference 0.38 (0.12-0.63) mmol l(-1), p = 0.01), respectively, for diabetic patients. The area under the glucose curve was greater after theophylline treatment for healthy control subjects (p = 0.0292) and for diabetic patients (p = 0.0241) but there were no concomitant significant increases in plasma c-AMP or in endogenous glucose production rate. Whether the increase in glucose recovery is large enough to suggest that chronic theophylline administration will protect against insulin-induced hypoglycaemia remains unsettled.     

Influence of puberty on endothelial dysfunction and oxidative stress in young patients with type 1 diabetes

OBJECTIVE: To examine the influence of puberty on endothelial dysfunction and oxidative stress in children and young people with type 1 diabetes. RESEARCH DESIGN AND METHODS: There were 51 young patients with type 1 diabetes, including 12 prepubertal children, 16 adolescents, and 23 young adults who had no clinical diabetic angiopathy, studied; none had microalbuminuria. The three groups were matched for glycemic control, and systolic and diastolic blood pressures and cholesterol levels were not significantly different between the groups. Endothelium-dependent vasodilatation was assessed by laser Doppler flowmetry after iontophoresis of acetylcholine (ACh) to the skin of the dorsum of the right foot. Soluble E-selectin, intercellular cell adhesion molecule-1 (ICAM-1), von Willebrand factor (vWF), plasma thiol (PSH), red cell glutathione (GSH), and red cell superoxide dismutase (SOD) were measured in blood samples obtained in the early morning. RESULTS: Skin vascular responses to ACh were significantly reduced in the young adult group compared with the prepubertal group (P < 0.05, analysis of variance). The levels of soluble ICAM-1 and E-selectin were significantly higher in the adolescent group compared with the young adult group: 338 (267-415) and 89 (64-106) ng/ml (median [interquartile range]), respectively, versus 255 (222-284) and 58 (54-71) ng/ml (P < 0.01 and P < 0.005, Mann-Whitney U test). SOD levels were significantly higher in the prepubertal group at 250 (238-282) micro/ml, when compared with the adolescent, 217 (171-249) micro/ml (P < 0.04), and young adult, 217 (157-244) micro/ml (P < 0.02), groups. GSH tended to be lower in the adolescent group, 1,192 (1,047-1,367) micromol/l, when compared with the young adults, 1,286 (1,145-1,525) pmol/l, and levels of vWF tended to be higher in the adolescent group, but these failed to reach statistical significance (both P = 0.09). PSH was not different between the three groups. CONCLUSIONS: These results suggest that puberty modulates endothelial function and antioxidant mechanisms in childhood diabetes, which may have implications for therapy and intervention.     

Signal-averaged electrocardiogram in patients with insulin-dependent (type 1) diabetes mellitus with and without diabetic neuropathy

The medical charts and operative files of 112 patients (combined inception cohort) with well to moderately differentiated invasive glottic squamous cell carcinoma presenting fixation (22) or impaired motion (90) of the true vocal cord (TVC) consecutively treated with cricohyoidoepiglottopexy (CHEP) at our institutions from 1972 to 1989 were retrospectively reviewed. A minimum 5-year follow-up was always achieved. The Kaplan-Meier 5-year actuarial survival, local recurrence, nodal recurrence, distant metastasis, and metachronous second primary tumor estimate for the entire group of patients were 84.7%, 5.4%, 6.4%, 1.2%, and 10.8%, respectively. The 5-year absolute and cause-specific survival rates were 85.5% and 94.1% for patients with fixation of the TVC and 81.3% and 96% for patients with impaired motion of the TVC. The 5-year actuarial local control rates for patients with fixation or impaired motion of the TVC were 95.4% and 94.4%, respectively. Local recurrence was statistically more likely in patients with positive margins (p = .007). Nodal recurrence was statistically more likely in patients with local recurrence (p = .005). Permanent tracheostomy related to postoperative laryngeal stenosis was requested in 2 patients. Aspiration-related completion total laryngectomy and/or permanent gastrostomy were never requested. Overall, local control and laryngeal preservation were achieved in 97.3%, and 95.5% of patients, respectively. At our institutions, the change from the conservative treatment modalities of radiotherapy and vertical partial laryngectomy to CHEP has brought about an increase in long-term survival, local control, and laryngeal preservation rates when compared to historical controls using vertical partial laryngectomy or radiotherapy.     

Dermatoglyphics in type 1 diabetes mellitus

Although fingerprints and handprints are widely used in criminology, it is only recently that this approach has been applied to the field of medical and genetic diagnoses. In order to investigate dermatoglyphics in Type 1 diabetes mellitus, quantitative characteristics of fingers and palms (ridge count and main line indices) as well as qualitative parameters such as digital and interdigital patterns, the position of the palmar axial triradii and main line courses were analysed in 88 male and 108 female Type 1 diabetic patients and compared with data from 100 male and 99 female normal controls. Type 1 diabetic patients show a lower third finger ridge count (p < 0.05) and a-b ridge count (p < 0.001) and higher transversality of the main lines as indicated by the main line index value (p < 0.001) or the ending of the main line A in a specific sector 5, 5', and 5" (p < 0.001) compared with controls. In addition, diabetic patients show higher frequency of palmar axial t' and t" triradii (p < 0.001) and a lower frequency of 'true' patterns in the fourth interdigital and thenar area (p < 0.001) than controls. By multivariate analysis of quantitative and qualitative variables a predictive value of 78.6% and 77.3%, respectively, for male, and 81.4% and 82.2%, respectively, for female Type 1 diabetic patients was found. In conclusion, dermatoglyphics seem to be an interesting tool for genetic studies related to Type 1 diabetes.     

Three patients with insulin-treated diabetes and senile dementia of Alzheimer''s type

Caught between the successes of modern psychopharmacology, the requests of suffering patients for quick relief, and the shortsightedness of many third-party payers, psychodynamic psychotherapy might seem to be on the ropes. It is, however, thriving and providing crucial help to many individuals for whom medication and brief counseling are insufficient. Meanwhile, many more who could benefit from psychotherapy do not have an opportunity to do so. Although psychodynamic psychotherapy originated and developed within a medical framework, it has minimal visibility on the current medical scene, and many physicians have been provided with little meaningful information about it. This article is intended to give physicians a general idea of what psychodynamic psychotherapy is and how it works.     

Human atrial natriuretic peptide in patients with type 1 diabetes mellitus: is it related to the development of diabetic nephropathy?

There is controversy as to whether increased plasma levels of human atrial natriuretic peptide (hANP) in patients with type 1 diabetes mellitus may contribute to the development of diabetic nephropathy. Therefore, we decided to conduct two studies to examine the relationship of hANP levels to urinary albumin excretion and blood pressure. In a cross-sectional study, 83 randomly selected type 1 diabetic patients were investigated. 19 of the patients had increased urinary albumin excretion. 45 healthy volunteers served as controls. In a longitudinal study, 19 type 1 diabetic patients were examined for one year at monthly intervals. An increased risk of eventually developing diabetic nephropathy was identified in 7 out of these patients by repeatedly revealing increased urinary albumin excretion. On the average, hANP levels were increased in type 1 diabetic patients in comparison to controls (P < 0.001). In both studies, hANP levels were positively related (P < 0.05) to mean arterial blood pressure. There was no correlation between hANP levels and metabolic control. hANP levels lay within normal range irrespective of normal or elevated urinary albumin excretion provided that mean arterial blood pressure was normal. In the longitudinal study, increased urinary albumin and alpha-1-microglobulin excretion preceded the increase in both hANP levels and mean arterial blood pressure. Although hANP levels were evidently not related to the disease mechanisms of early diabetic nephropathy, it is tempting to speculate that hANP may contribute to the vicious circle connecting diabetic kidney disease to hypertension once that its levels are increased by elevated blood pressure.     

Using behavioral interventions to assist children with type 1 diabetes manage blood glucose levels.

Treatment and management of chronic disease processes on children occurs across multiple settings, placing demands for consultation and expertise on school personnel, including school psychologists. One such chronic condition in children is type I diabetes. Children with type I insulin dependent diabetes mellitus exhibit high rates of noncompliance to treatment, which can lead to a variety of medical problems. This study examined the effectiveness of a specific behavioral intervention using behavioral consultation (BC) and conjoint behavioral consultation (CBC) to reduce uncontrolled blood glucose levels in medically at-risk children. An intermittent reward procedure was utilized to reinforce individualized target behaviors associated with treatment noncompliance. Specific target behaviors were individually established for six patients ages 8-12 through behavioral consultation interviews. Each child was randomly assigned to a reward + BC or reward + CBC condition. Results of the study showed that all participants improved; with slightly greater gains shown in the CBC condition. Follow-up data for 3 of the 4 participants completing the study showed improved compliance and mental health status. Treatment acceptability date indicate the intervention was viewed positively by parents and school based nurses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Characterization of insulin autoantibodies in relatives of patients with type I diabetes

We studied in detail the anti-insulin autoantibodies in 29 nondiabetic relatives of patients with type I diabetes. The affinity of the autoantibodies for [125I]human insulin was high (1.34 x 10(9)-20.71 x 10(9) L/mol), and the capacity was low (0.84 x 10(-12)-37.80 x 10(-12) M). The product of affinity x capacity of each relative's antibodies directly correlated (r = 0.99) with the level of antibodies determined in our standard radioassay. The autoantibodies from each of the subjects studied had the same rank order of affinities for insulin from different species. Guinea pig, fish insulin, and insulin containing Trp rather than Leu in position 13 of the A-chain inhibited minimally the human insulin binding. Human proinsulin, insulin containing Gln rather than Glu in position 17 of the A-chain, and desoctapeptide insulin (des B23-30) all inhibited binding effectively. Insulin autoantibodies in relatives of patients with type I diabetes share common epitope(s), which suggests a common pathogenic mechanism for production of such antibodies. The epitopes from this initial analysis appear to include amino acids B1-B3 and A8-A13. The region recognized can be distinguished from the insulin receptor binding domain.