Changes in attention with hypo- and hyperglycaemia in children with insulin dependent diabetes mellitus

We compared the results of a computerized attention test (TOVA) in 38 children with insulin dependent diabetes mellitus in relation to various spontaneously occurring blood glucose levels. Testing was performed at the following blood glucose levels: <3.3 mmol/1 (hypoglycaemia), 3.3-8.3 mmol/1 (normoglycaemia) and >8.3 mmol/1 (hyperglycaemia). The attention (sum of errors and response time) varied significantly with the blood glucose level (P = 0.002). The highest number of errors of omission and the longest response time was observed during the test run with hypoglycaemia. Age, sex, age at manifestation of the disease, metabolic control and the results of the intelligence test had no significant influence on these results. We found that attention in children with diabetes was significantly reduced compared to TOVA norms especially during mild hypoglycaemia (P < 0.001). Irrespective of the blood glucose levels, reaction time and the variability of the reaction time differed significantly between TOVA norms and diabetic children (P < 0.01). CONCLUSION: In children with diabetes mellitus a significant reduction in attention was found at mild hypoglycaemia but as well at low normal blood glucose levels. Attention deficits due to transient lowering of blood glucose may therefore occur in diabetic children even before they are aware of hypoglycaemic symptoms.     

Urinary excretion of extracellular matrix proteins in insulin dependent diabetes mellitus

The purpose of the study was to assess urinary excretion of extracellular matrix proteins and proteolytic enzymes in 12 subjects with IDDM with albuminuria, 12 subjects with IDDM without microalbuminuria and 10 normal healthy subjects. Urinary excretion of FN was significantly higher in subjects with IDDM and albuminuria as compared to patients with IDDM without microalbuminuria and healthy subjects (223.6 +/- 143.2 vs. 103.2 +/- 59.7 vs. 58.3 +/- 12.0 ng/mg creatinine, p < 0.01). Urinary level of type IV collagen was significantly elevated in subjects with IDDM and albuminuria as compared to IDDM without microalbuminuria and healthy subjects of cathepsin B was significantly higher in diabetic patients with albuminuria as compared to patients without microalbuminuria and healthy subjects (0.82 +/- 0.53 vs. 0.25 +/- 0.17 vs. 0.22 +/- 0.05 mlU/mg creatinine, p < 0.01). Urinary activity of plasmin was significantly elevated in diabetic patients with albuminuria as compared to subjects without microalbuminuria and healthy control (0.477 +/- 0.37 vs. 0.194 +/- 0.09 vs. 0.21 +/- 0.02 mlU/mg creatinine, p < 0.01). Our data indicate that increase in the urinary excretion of extracellular matrix proteins may be the useful tool for monitoring glomerular injury.     

Incidence of insulin dependent diabetes mellitus in children of Shanghai, China

Seven patients with seven acute slipped capital femoral epiphyses (SCFE) had computed tomography (CT) scan determination of femoral version. Version value differences were compared between the involved and uninvolved sides, and each was compared with a standard value for age. Comparison was also made with chronic slipped femoral version values. As compared to the standard of 20 degrees, the acute, involved side femoral version was 9.3 degrees (p = 0.057). Comparisons of involved and uninvolved sides showed no significant difference (p = 0.25). Analysis of differences of bilateral femoral version of patients with acute SCFE with that of patients with chronic SCFE version showed a significant difference (p = 0.009). Version in patients with acute SCFE more closely resembles the normal value than does that of patients with chronic SCFE, further emphasizing the uniqueness of the acute type of SCFE.     

Factors involved in noncompliance with drug treatment in non-insulin dependent diabetes mellitus

OBJECTIVE: To find the level of non-compliance with treatment with oral hypoglycemics, its causes and the profile of non-compliant patients. DESIGN: Prospective study. SETTING: Primary Care Centres in the province of Alicante. PATIENTS: 107 diabetics not dependent on insulin on the lists of five General Medicine practices and all receiving pharmacological treatment. MEASUREMENTS AND MAIN RESULTS: The method used to value compliance was a surprise count of pills in the patient's home. Patients achieving 80-110% compliance were considered compliant. The level of non-compliance was 51.5% (C.I. 42.1%-61%), 36.5% being hypocompliers and 15% hypercompliers. Forgetting (40.7%) and lack of knowledge (29.5%) were the most frequent reasons for non-compliance. The factors associated with non-compliance were: over four years evolution of the disease (p = 0.02), the diet not properly observed (p = 0.03), over a year in regular treatment (p = 0.006), poor control of the disease valued by HbA1C (p = 0.003). CONCLUSIONS: A high level of non-compliance with pharmacological treatment was found for patients with Diabetes Mellitus not dependent on insulin. Its causes were identified and factors associated with poor compliance were profiled.     

Use of a computer for the optimal results of treatment of diabetes mellitus with insulin

The authors present material on the optimization of diabetes mellitus treatment, with the aid of a computer. There were 320 patients under observation. Mathematical models describing the process of the patients treatment and permitting to pronosticate the blood and urine sugar level during the treatment were developed. The use of the imitation experiment on a computer permitted to test several therapeutic variants for the given patient and to choose the optimum one, leading to the most rapid compensation. The second task consisted in the maintenance in the patients of blood glucose variations within definite limits, in the course of 24 hours. An individual model of blood glucose dynamics in the course of 24 hours is set on the computer, and then the optimal scheme of insulin treatment is chosen. Practical testing of such scheme showed its efficacy.     

Enterovirus infections and insulin dependent diabetes mellitus--evidence for causality

BACKGROUND: Insulin-dependent diabetes mellitus (IDDM) has a long subclinical period characterised by gradually progressing autoimmune damage of insulin producing beta-cells. Clinical IDDM is manifested when 90% of beta-cells have been destroyed. Several studies have indicated that enterovirus infections, coxsackievirus B (CVB) infections especially, are frequent at the manifestation of clinical IDDM suggesting that they can precipitate the symptoms of IDDM in individuals who already have an advanced beta-cell damage. Recently, the first prospective studies have been published suggesting that enterovirus infections can also initiate the process several years before clinical IDDM. This implies that enterovirus infections may have a crucial role in the pathogenesis of human IDDM. OBJECTIVE: The recent findings have brought up the question whether the time has come when a causal association between enterovirus infections and IDDM could finally be confirmed. This review focuses on this question summarising the current knowledge and the prospects of future research. STUDY DESIGN: Review of the recent progress in studies evaluating the role of enterovirus infections in human IDDM. CONCLUSIONS: The currently available information supports the assumption that the role of enterovirus infections may be more important than previously estimated. Enterovirus infections are obviously associated with increased risk of IDDM, but whether this association reflects causal relationship remains to be confirmed in future studies. Prospective birth-cohort studies will be among the most important ones giving important data on the etiologic fraction of enterovirus infections, the properties of diabetogenic virus variants and the mechanisms of beta-cell damage.     

Glycosylated hemoglobin and fetal growth in normal, gestational and insulin dependent diabetes mellitus pregnancies

Aims of the study were: evaluation of HbA1c levels in the peripheral blood of pregnant women with insulin dependent diabetes, gestational diabetes, glucose intolerance, and healthy pregnant controls; implications of HbA1c concentration on detection and the control of women with impaired carbohydrate metabolism in pregnancy; comparison of HbA1c levels with appearance of miscarriages, and premature deliveries; comparison of weight gain during pregnancy to HbA1c levels; comparison of difference from ideal body weight with HbA1c in diabetic pregnant women; comparison of neonatal birth weight and HbA1c levels. 290 pregnant women were enrolled to the study. The highest value of HbA1c was in the group IDDM pregnant women (7.7% +/- 1.8%), and the lowest value of HbA1c was in the control group (4.1% +/- 0.5%). Statistically significant coefficients were found between HbA1c and weight gain during pregnancy, between weight deviation from ideal body weight and HbA1c (r = 0.54 and r = 0.48 respectively); and between newborns weight and HbA1c (r = 0.51). Well regulated glycemia and intensive pregnancy follow-up of diabetic women reduces stillbirths, neonatal complications and neonatal macrosomia incidence.     

Anserine bursitis and non-insulin dependent diabetes mellitus

OBJECTIVE: To determine the relationship between non-insulin dependent diabetes mellitus (NIDDM), knee pain, and anserine bursitis, and its relation to sex, age, or body mass index (BMI). METHODS: Ninety-four consecutive patients with NIDDM, 66 women and 28 men, and 57 nondiabetic patients, 36 women and 22 men, were examined at an outpatient clinic of a tertiary care hospital. Date of onset in patients with NIDDM was noted, and serum was analyzed for either hemoglobin A1C (HbA1C) or glycosylated hemoglobin (GHb) in 69 of these patients. Anserine bursitis was diagnosed if knee pain and tenderness at the bursal site were found on examination. RESULTS: On examination 34 (36%) patients with NIDDM were found to have anserine bursitis. Of these, 31 (91%) were women and 3 (9%) were men (p < 0.05). Age, BMI, duration of diabetes, HbA1C or GHb, and age of onset of diabetes were found not to differ significantly between patients with and those without anserine bursitis. CONCLUSION: A relationship exists between NIDDM, knee pain, and anserine bursitis unrelated to age, BMI, duration and control of diabetes, and age at the diagnosis of diabetes.     

Periodontal findings in elderly patients with non-insulin dependent diabetes mellitus

The periodontal status of 25 patients with non-insulin dependent diabetes mellitus (NIDDM) (age range 58 to 76) was investigated and compared with 40 non-diabetic control subjects (age range 59 to 77). Surfaces with visible plaque and bleeding after probing, calculus, recessions, and pathological pockets were examined. The total attachment loss was calculated as a sum of recessions and pockets in millimeters. Mesial and distal bone loss was measured from panoramic radiographs and mean alveolar bone loss was calculated. Periodontal disease was considered advanced when mean alveolar bone loss was over 50%, or 2 or more teeth had pockets > or = 6 mm. Microbiological analysis comprised the detection of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Bacteroides forsythus by a polymerase chain reaction (PCR) method. Patients with NIDDM had significantly more often advanced periodontitis than control subjects, 40.0% and 12.5%, respectively. Diabetic patients did not harbor more pathogens than the control subjects. The HbA1C level deteriorated in patients with advanced periodontitis, but not in other patients with NIDDM, when compared to the situation 2 to 3 years earlier. Advanced periodontitis seems to be associated with the impairment of the metabolic control in patients with NIDDM, and a regular periodontal surveillance is therefore necessary.     

Homozygous parent affected sib pair method for detecting disease predisposing variants: application to insulin dependent diabetes mellitus

For complex genetic diseases involving incomplete penetrance, genetic heterogeneity, and multiple disease genes, it is often difficult to determine the molecular variant(s) responsible for the disease pathogenesis. Linkage and association studies may help identify genetic regions and molecular variants suspected of being directly responsible for disease predisposition or protection, but, especially for complex diseases, they are less useful for determining when a predisposing molecular variant has been identified. In this paper, we expand upon the simple concept that if a genetic factor predisposing to disease has been fully identified, then a parent homozygous for this factor should transmit either of his/her copies at random to any affected children. Closely linked markers are used to determine identity by descent values in affected sib pairs from a parent homozygous for a putative disease predisposing factor. The expected deviation of haplotype sharing from 50%, when not all haplotypes carrying this factor are in fact equally predisposing, has been algebraically determined for a single locus general disease model. Equations to determine expected sharing for multiple disease alleles or multiple disease locus models have been formulated. The recessive case is in practice limiting and therefore can be used to estimate the maximum proportion of putative susceptibility haplotypes which are in fact predisposing to disease when the mode of inheritance of a disease is unknown. This method has been applied to 27 DR3/DR3 parents and 50 DR4/DR4 parents who have at least 2 children affected with insulin dependent diabetes mellitus (IDDM). The transmission of both DR3 and DR4 haplotypes is statistically different from 50% (P < 0.05 and P < 0.001, respectively). An upper estimate for the proportion of DR3 haplotypes associated with a high IDDM susceptibility is 49%, and for DR4 haplotypes 38%. Our results show that the joint presence of non-Asp at DQ beta position 57 and Arg at DQ alpha position 52, which has been proposed as a strong IDDM predisposing factor, is insufficient to explain the HLA component of IDDM predisposition.     

Systematic screening for diabetic eye disease in insulin dependent diabetes

It has been demonstrated that alveolar macrophages (AM) are permissive for human immunodeficiency virus (HIV-1) after in vitro infection. However, data concerning in vivo infection of AM by HIV-1 still conflict. Therefore, we investigated AM collected by bronchoalveolar lavage from 15 HIV-1-infected patients. HIV-1 p24 and Gp120 antigens and viral RNA were not detected by immunocytochemistry and in situ hybridization, respectively, using 35S-labeled 3 kb Pol-Env, 0.350 kb Gag, and 0.150 kb U5 LTR cRNA probes. In contrast, when using polymerase chain reaction on DNA extracted from purified AM, HIV-1 DNA was detected in the seven patients tested. After short-term culture of alveolar cells from three HIV-1-infected patients and in vitro stimulation with granulocyte/macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha), HIV-1 replication was observed in most of the AM. These results demonstrate that AM are latently infected by HIV-1 in vivo but are not a site for viral replication. In contrast, HIV-1 replication occurs when AM are withdrawn from their local environment, enhanced by GM-CSF and TNF-alpha stimulation. This suggests either a negative control or an inadequate stimulation of HIV-1 replication in the alveolar environment.     

Quantitative morphology of the rat kidney during diabetes mellitus and insulin treatment

A morphometric study was performed on moderately hyperglycaemic streptozotocin diabetic rats after 10 and 50 days of diabetes, and on groups of rats that, after initial hyperglycaemia for 50 days, were insulin treated for 2 h or for 5, 15 or 38 days. A group of hyperglycaemic diabetic animals were fasted for 18 h. Another group of rats had acute hyperglycaemia induced by intravenous glucose injection. After 10 and 50 days of diabetes, kidney weight was increased by 55 and 93%. Glomerular volume, tubule length, and tubular and interstitial volume increased in diabetic animals compared with controls. After 4 h insulin treatment, the kidney weight was 20% decreased; after 5 days it was 31% decreased. After 38 days the kidney weight was still 26% greater than in controls. In diabetic animals, 18 h fasting induced a 30% decrease in kidney weight. In normal animals, acute hyperglycaemia induced a 22% increase in kidney weight. Volume fractions of most kidney structures remained similar in all groups. However, the glomerular volume fraction was smaller during kidney enlargement, and the tubular volume fraction was larger after induced hyperglycaemia compared with controls. In conclusion, high blood glucose levels in diabetic and normal animals are associated with increased kidney weight. In hyperglycaemic diabetic animals, normalization of blood glucose after insulin treatment or fasting was followed by a decrease in kidney weight.     

Pedigree investigation of familial non-insulin dependent diabetes mellitus

To discuss the inheritant mode of familial NIDDM. METHODS: According to WHO criteria of DM, 100 NIDDM Probands with family history of DM were diagnosed and 100 persons were chosen at random for controls. The survey of DM was performed in both groups, including FBG, HbAlc, FINS. Some members had insulin release test. RESULTS: The prevalance rates of DM in familial DM group were 26 times of the control group (34.3% and 1.3%). The prevalance rate of DM among first-degree relation was 18 times higher than that in general population (28.3% and 1.5%). The rate of diabetes in the siblings and in the off-springs was 44.4% and 9.7% respectively. The pedigree analyses showed that 83.9% affected families had one diabetic parent, one half siblings had DM, and there was a successive transmission of DM through at least three generations in sixteen large families. Besides, the incidence of DM was much higher in females than in males (40% and 28%). Among affected parents, diabetlic mothers were much more than diabetic fathers (50.8% and 27.6% P < 0.01). CONCLUSION: Familial NIDDM had a familial aggregation. It was inherited in the manner of Mendelian autosomal dominant inheritance. The difference between the rate in DM mothers and fathers was probably due to unequal prevalance rate in females and males.     

Indication and results of insulin therapy for gestational diabetes mellitus

The aim of this study was to determine whether amniotic fluid insulin concentration (AFI) is a better parameter than mean maternal blood glucose values (MBG) for deciding about insulin therapy in patients with gestational diabetes. MBG's were calculated on the base of 9 blood glucose levels during a 24 hour period after one week of diet therapy. In a prospective trial between 1987 and 1989 in Karlsburg, 123 gestational diabetic patients were randomized into two groups. Treatment was either based on the concentration of AFI or MBG levels. In a second series in Berlin, 103 patients were offered amniocentesis. 81 patients agreed and 22 refused. Treatment was then analogous to that in Karlsburg. In both groups of the randomized population, strict metabolic control was achieved. There was no difference regarding pregnancy complications. Earlier labor induction and higher cesarean section rates were seen in the non-invasive group (p < 0.05). The incidence of diabetic fetopathy and neonatal hypoglycemia was significantly lower in the invasive group (p < 0.01), even though the metabolic control parameters did not differ between the two groups. The results in Berlin correspond to these findings. In conclusion, AFI enables the recognition of any hyperinsulinism reaction to the maternal metabolic situation. We recommend the additional measurement of the AFI concentration between 28 and 36 weeks as the direct fetal parameter for deciding about insulin treatment.     

Insulin sensitivity and insulin response in women with gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is associated with much increased risk of developing diabetes later on in life. Using the frequently sampled intravenous glucose tolerance test and the minimal model analyses we have therefore determined the early insulin response to glucose (EIR) and insulin sensitivity (Si), in women with GDM of different severity (n = 14) and in normal women (n = 10). During the last trimester of pregnancy. GDMs compared to controls had significantly lower EIR (p < 0.001) and Si (p < 0.01). The reduction in EIR was less marked in GDM patients treated with diet alone (n = 6) as compared to GMD patients (n = 8) who subsequently during pregnancy needed treatment also with insulin. The insulin treated GDM group only had higher fasting glucose level than controls (5.2 vs 4.2 mmol/l, p < 0.001). Both GDM subgroups had slightly elevated basal levels of FFA and 3-hydroxybutyrate. Si and EIR were inversely correlated in control women and their fasting glucose correlated both to EIR (r = 0.63, p < 0.05) and to Si (r = 0.59, p < 0.05). In the GDM subgroups Si and EIR were unrelated and there were no correlations between fasting glucose and Si or EIR. These results suggest that glucose intolerance in GDM patients in the last trimester of pregnancy is characterized by both an impaired insulin secretion and an increased resistance to insulin. The impairment of insulin secretion and action increases with the severity of hyperglycemia, and the relative insulin deficiency characterizing GDM patients is associated with a selected defect in insulin action mainly affecting gluco-regulation.