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.     

Somatic mosaicism in a patient with neurofibromatosis type 1

Using loss of heterozygosity analysis, a method designed to detect moderate to large gene deletions, we have identified a new-mutation neurofibromatosis type 1 (NF1) patient who is somatically mosaic for a large maternally derived deletion in the NF1 gene region. The deletion extends at least from exon 4 near the 5' end of the gene to intron 39 near the 3' end. The gene-coding region is, therefore, mostly or entirely deleted, encompassing a loss of > or = 100 kb. We hypothesize that the deletion occurred at a relatively early developmental timepoint, since signs of NF1 in this patient are not confined to a specific body region, as seen in "segmental" NF, and since both mesodermally and ectodermally derived cells are affected. This report provides the first molecular evidence of somatic mosaicism in NF1 and, taken together with a recent report of germ-line mosaicism in NF1, adds credence to the concept that mosaicism plays an important role in phenotypic and genetic aspects of NF1 and may even be a relatively common phenomenon.     

A case of chorea-acanthocytosis associated with low glycohemoglobin A1c

We reported the first case of chorea-acanthocytosis associated with low glycohemoglobin A1c. Fasting blood sugar, daily profile of blood sugar, serum fructosamine and 75 g glucose tolerance test were all within normal limits. While abnormal hemoglobins were not detected, red blood cell half-life was sharply reduced to 13.4 days. These findings suggest that the low glycohemoglobin A1c in this case is highly ascribable to the reduction of red blood cell half-life rather than to continuous hypoglycemia. However, we can not rule out that the abnormalities of red blood cell membrane, suggested factors in this disease, may be related to the low glycohemoglobin A1c value. Further investigations on chorea-acanthocytosis cases with normal red blood cell half-life are necessary in order to elucidate whether an abnormal glycohemoglobin A1c value is a specific indication regarding this disease.     

Risk factors for cardiovascular disease in children with type I diabetes: Part 1

This study characterizes the pharmacokinetics of bumetanide after an intravenous dose of 0.05 or 0.10 mg/kg to 14 neonates (weight range 820-4,000 g; gestational age 26-40 weeks) during the first week of life. Blood samples and urine were collected for up to 12 h after dosing. Estimated serum clearance was 0.2-1.0 ml/min.kg (range), volume of distribution was 0.22 l/kg (range 0.11-0.32 l/kg), and the harmonic mean half-life was 6-7 h (range of 4-19 h). Nonrenal clearance accounted for 58-97% of the serum clearance with the presence of certain oxidative metabolites of bumetanide in the urine. These findings suggest higher dosing requirements and prolonged intervals as compared to adults. Utilizing these pharmacokinetic data, pharmacodynamic and ototoxicity studies should be conducted to establish a safe and effective neonatal dose.     

Evaluation of an immunoturbidimetric assay for haemoglobin A1c on a Cobas Mira S analyser

A case-control study was carried out in Spain to assess associations between parity, lactation and age at first full-term pregnancy and breast cancer. From November 1989 to February 1992, 184 incident breast cancer histologically confirmed cases were interviewed and matched by age and residence to 184 hospitalized patients and 184 community controls selected by random digit dialing. Multiple logistic regression was used to assess the independent influence of each factor on the risk of breast cancer in relation to other factors included in the model. Age at first full-term pregnancy was associated with breast cancer risk with an estimated odds ratio of 3.5 (95% CI 1.41-9.83) for women with their first birth after 30 years in comparison with those whose first birth was before age 21. Breast cancer risk decreased with increasing number of full-term pregnancies, OR 0.3 (95% CI 0.16-0.78) for women who had had more than 3 full-term pregnancies in comparison with nulliparous women. Among parous women, the estimated OR for women with more than 3 children was 0.4 (95% CI 0.13-0.81) after allowance for age at first childbirth and lactation. The estimated OR was 2.6 (95% CI 1.4-4.7) for women with a positive history of breast cancer in first-degree relatives. Breast cancer was not associated with total duration of lactation. The study indicates that parity is an independent risk factor associated to breast cancer and that the women with a late age at first full-term pregnancy constitute a high-risk group.     

Comparison of advanced glycation endproducts on haemoglobin (Hb-AGE) and haemoglobin A1c for the assessment of diabetic control

In a pilot study (1997) using POTENS+, our coagulation instrument, we determined that: (a) an Anticoagulant Therapy Factor (ATF) was comparable to the International Normalized Ratio (INR) for monitoring warfarin anticoagulant therapy, (b) one could use any of the four thromboplastins with which the ATF was derived with comparable results, and (c) the ATF could be proposed to monitor warfarin therapy. The ATF-INR comparisons correlated well statistically; but when individual ATF-INR comparisons were later studied, there were frequent discrepancies. The pilot study (1997) was based on hospitalized patients, so almost all patients were undergoing induction of warfarin anticoagulation. Since none of them had taken warfarin for at least six weeks, none of them could be considered "stable" on warfarin. In the present study, all patients were on warfarin therapy for at least six weeks, and the ATF equation was modified by multiplying it by the prothrombin ratio (PR) to give a corrected ATF (CATF). This CATF was then further modified to achieve agreement with the INR by adjusting the linear regression line by means of analytic geometry, so that the CATF-INR regression line now had a slope of one and passed through the origin. With these changes, the modified ATFs (MATF) and INRs correlated well and were nearly equal numerically when using two of the four thromboplastins. Reason for the discrepancies with the other two thromboplastins will be discussed.     

Evidence for a structural mutation of procollagen type I in a patient with the Ehlers-Danlos syndrome type VII

We have found that the collagen from a patient with the Ehlers-Danlos syndrome type VII contained a polypeptide chain, pN alpha 2, not present in collagen prepared from normal tissue. Fibroblasts cultured from the patient's skin produced type I procollagen in which the NH2-terminal propeptide of pro alpha 2 was cleaved to about half of normal values by chick procollagen neutral protease which removes the NH2-terminal propeptides from procollagen (N-protease). The NH2-terminal propeptide on the pro alpha 2 chain of the patient's procollagen was also more resistant than procollagen from control fibroblasts to digestion by pepsin or alpha-chymotrypsin. assays for procollagen N-protease indicated that the patient's fibroblsts contained about the same level of enzymic activity as normal fibroblasts. These results suggest that the patient's fibroblasts synthesize both an abnormal pro alpha 2 chain and a normal pro alpha 2 chain. The abnormality probably consists of a structural mutation in or near the site at which procollagen N-protease cleaves the pro alpha 2 chain. The results presented here appear to provide the first example of a mutation in a structural gene for collagen. Since equal amounts of pN alpha 2 and alpha 2 are found in the protein in neutral salt extracts of the patient's tissue, as well as in newly synthesized collagen produced by cultured skin fibroblasts, and since both parents are phenotypically normal and express exclusively normal collagen chains, the patient is likely to be a sporadic heterozygote, arisen by new mutation, with one normal and one abnormal gene coding for pro alpha 2.     

Seven years of remission in a type I diabetic patient

OBJECTIVE: To analyze factors contributing to a long-term remission in a patient with type I diabetes. RESEARCH DESIGN AND METHODS: The patient was treated with cyclosporin for 16 mo after a short duration of symptoms. During the 7-yr follow-up, we tracked his glycemic control, oral glucose tolerance, insulin sensitivity, endogenous insulin secretion, and beta-cell immunology. The results are compared with those of matched diabetic patients and healthy control subjects. RESULTS: Insulin therapy was discontinued after 5 wk. Thereafter the patient had normal fasting and home blood glucose concentrations and near-normal HbA1c without insulin therapy for 7 yr. During this period, he maintained islet cell antibodies, although his basal and glucagon-stimulated C-peptide concentrations were normal. He participated in active physical training and had an insulin sensitivity higher than in sedentary control subjects or trained diabetic patients and equal to that in healthy athletes. His oral glucose tolerance decreased gradually and became diabetic during the last 3 yr. CONCLUSIONS: In this patient, an early start of cyclosporin therapy probably contributed to the maintenance of endogenous insulin secretion, and insulin sensitivity was high because of physical training. Consequently, the patient was able to maintain normoglycemia without exogenous insulin therapy for 7 yr.     

Extradural anaesthesia for caesarean section in a patient with syringomyelia and Chiari type I anomaly

We describe elective Caesarean section performed under extradural anaesthesia in a parturient with symptomatic syringomyelia and coexisting Chiari type I anomaly. Syringomyelia is reviewed and the anaesthetic implications of the condition discussed. Anaesthesia should be directed primarily at avoidance of increased intracranial pressure, which can cause sudden deterioration in these patients.     

A novel nonsense mutation associated with an exon skipping in a patient with hereditary protein S deficiency type I

The genetic defect in a patient with hereditary type I protein S (PS) deficiency was investigated. All the exons and intron-exon junctions of the patient's PS gene were amplified by PCR and subjected to heteroduplex screening. Only the PCR product of exon 4 revealed heteroduplex bands. A novel nonsense mutation, Ser62 (TCA) to Stop (TGA) was found in exon 4. RT-PCR detected the aberrant mRNA in the patient's platelets, which was markedly reduced in amount and lacked the region of exon 4, suggesting that the nonsense mutation affected the mutated mRNA metabolism and induced exon skipping. The skipping of exon 4 causes an in-frame deletion of 29 amino acids which just construct the thrombin-sensitive region of the PS molecule. The loss of such an important domain as well as the quantitative decrease in the mutated mRNA appear to be responsible for the type I PS deficiency in this patient.     

Clinical case of the month. Galloping nephropathy in a patient with type 2 diabetes

Thirteen surgical patients affected by colorectal cancer have been evaluated to study the effectiveness of a short-term preoperative therapy with interleukin-2 (IL-2). Seven patients have been treated for three days before surgery with subcutaneous administration of IL-2 (9.000.000 U.I. b.i.d.). Six patients have been treated with placebo and have been considered as control group. All the patients have been operated upon 36-48 hours after the last administration of IL-2 or placebo. The assays of CD-3+, CD-4+, CD-8+ e CD-56+ lymphocytes, evaluated preoperatively and 7 days after the operation, have showed a postoperative increase of CD8+ and CD56+ and a decreased ratio of CD4+/CD8+. The results of this study, although not conclusive, suggest a positive antitumoral response in patients treated preoperatively with IL-2. Further studies could be performed to evaluate the survival after such a treatment.     

Drug clinics. How I treat a patient with a low concentration of HDL cholesterol

The decision to treat an individual with low HDL cholesterol level depends on his overall cardiovascular risk profile and the therapeutic strategy is based upon the characteristics of the lipid profile (isolated abnormality, associated hypertriglyceridaemia or combined elevation of LDL cholesterol). The treatment must favour diet and exercise, before considering a possible pharmacological approach. Results are usually acceptable with better life habits and appropriate diet when low HDL cholesterol level is associated to hypertriglyceridaemia. From a pharmacological point of view, the best results are obtained with fibrates or nicotinic acid. However, results are often disappointing when low HDL cholesterol level is isolated.     

Hemoglobin A1c in diabetes related to pregnancy induced hypertension

OBJECTIVE: To test the hypothesis that the poor control of diabetes during pregnancy is correlated with a high rate of pregnancy induced hypertension (PIH). METHODS: A retrospective analysis on 146 pregnant women with diabetes mellitus of White's class B to RF (gestational diabetes was excluded) diagnosed before pregnancy was carried out in Yale-New Haven hospital, U.S.A. RESULTS: 36.3% of the diabetic women developed PIH. Hemoglobin A1c (HbA1c) levels were higher than normal in 63.7% (93 cases) of the patients during their initial prenatal visits. In the group with HbA1c score > or = 6 and White's Class D-RF, more cases developed PIH than that in groups with HbA1c score < 6 and White's Class B and C (P < 0.01, P < 0.05). CONCLUSION: Diabetic women with high HbA1c score or advanced White's Class during pregnancy were at increased risk for PIH. Good control of blood glucose level throughout pregnancy may reduce the risk of PIH in diabetic women.     

Wound healing process differences in type I and type II diabetes mellitus

In 88 patients with purulent wounds in diabetes mellitus the course of wound healing was studied depending on the type of the disease. Clinical and morphological distinctions of the wound process in type 1 and type 2 diabetes mellitus were revealed.     

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.     

The association between a family history of type 2 diabetes and coronary artery disease in a type 1 diabetes population

The plasma protein beta2-glycoprotein I (beta2-GPI) is a major target of autoantibodies in patients with the antiphospholipid syndrome. To understand the physiological function of beta2-GPI and its potential role in the pathophysiology of the antiphospholipid syndrome, the binding of beta2-GPI to phospholipid membranes was characterized. The interaction of beta2-GPI with unilamellar vesicles containing varying amounts of acidic phospholipids with phosphatidylcholine (PC) was measured at equilibrium via relative light scattering. Analysis of binding isotherms gave apparent Kd values ranging from approximately 5.0 to 0.5 microM over a range of 5-20 mol % anionic phospholipid. Inhibition of binding by increasing ionic strength and Ca2+ ions suggests that binding is primarily electrostatic. These data indicate that beta2-GPI binding to membranes with physiological anionic phospholipid content is relatively weak in comparison to plasma coagulation proteins, suggesting that beta2-GPI does not function as a physiological anticoagulant based on its phospholipid-binding properties.     

Insulinoma in a patient with non-insulin-dependent diabetes mellitus

Insulinoma in a patient with pre-existing diabetes is exceedingly rare. Only a small number of well-documented cases have been reported in the world during the last 40 years. We describe a case with non-insulin-dependent diabetes mellitus who after seven years of sulfonylurea treatment experienced recurrent episodes of hypoglycemia. Endogenous hyperinsulinism was found and radiographical examination and transhepatic venous sampling confirmed an insulin secreting pancreatic tumor. After surgical excision of the tumor, patient was relieved from hypoglycemic attacks but required to initiate insulin injection for the treatment of hyperglycemia.     

Family functioning processes and diabetic ketoacidosis in youths with type I diabetes.

Purpose/Objective: To examine relations between episodes of diabetic ketoacidosis (DKA) and parental warmth, parental negativity, and lack of responsibility for diabetes-related tasks in a sample of youths with Type 1 diabetes (T1D). Research Method/Design: 100 youths with T1D and their caregivers, recruited from an inpatient diabetes unit and an outpatient diabetes clinic, participated. Participants completed disease-specific measures of family functioning (e.g., parental warmth, parent and child perceptions of negativity, family responsibility for diabetes regimen), and medical information (e.g., glycosylated hemoglobin and incidences of DKA) was obtained from medical records. Results: Results showed that higher child perceptions of parental warmth and caring related to the regimen were associated with decreased odds of experiencing a DKA episode. Child reports of higher parental negativity about the regimen were associated with increased odds of experiencing a DKA episode. Reports of who in the family was responsible for the diabetes regimen were not related to episodes of DKA. Conclusions/Implications: Findings suggested that family factors play a significant role in the occurrence or absence of DKA in children's long-term management of diabetes. Future intervention efforts should focus on warmth, caring, and negativity when children and their parents are problem solving and communicating about the diabetes regimen. (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.