Diagnosis and classification of diabetes mellitus: new criteria

New recommendations for the classification and diagnosis of diabetes mellitus include the preferred use of the terms "type 1" and "type 2" instead of "IDDM" and "NIDDM" to designate the two major types of diabetes mellitus; simplification of the diagnostic criteria for diabetes mellitus to two abnormal fasting plasma determinations; and a lower cutoff for fasting plasma glucose (126 mg per dL [7 mmol per L] or higher) to confirm the diagnosis of diabetes mellitus. These changes provide an easier and more reliable means of diagnosing persons at risk of complications from hyperglycemia. Currently, only one half of the people who have diabetes mellitus have been diagnosed. Screening for diabetes mellitus should begin at 45 years of age and should be repeated every three years in persons without risk factors, and should begin earlier and be repeated more often in those with risk factors. Risk factors include obesity, first-degree relatives with diabetes mellitus, hypertension, hypertriglyceridemia or previous evidence of impaired glucose homeostasis. Earlier detection of diabetes mellitus may lead to tighter control of blood glucose levels and a reduction in the severity of complications associated with this disease.     

Manifestation of diabetes (author's transl)]

Material of research: 350 cases of diabetes mellitus. The time between the manifestation of diabetes mellitus and the onset of retinopathy is reduced in two cases: with diabetes manifesting itself (a) at the age of puberty, (b) after the age of fifty. The retinopathy appears as "retinopathia simplex" (in all its different subvarieties) and as "retinopathia proliferans". Out investigation showed a gradual decrease in the benign forms of the retinopathia simplex with advancing years--from twenty to sixty--of diabetic manifestation, with retinopathia proliferans simultaneously gaining ground. With diabetes manifesting from sixty on, retinopathia proliferans dwindles to insignificance; there remains an indefinite form of retinopathia simplex.     

Diabetes research in South Carolina: past, present, and future

Medical investigators in South Carolina have been on the "cutting edge" of diabetes research for a number of decades. Despite this fact, our state ranks second in the nation in diabetes prevalence, and diabetes complications are more severe here than anywhere else. It is from the efforts of these investigators that our hope for a brighter future comes. Through a concerted effort toward prevention, improvements in care, and investigation of the pathophysiology of diabetes and its complications, researchers may reduce the substantial burden of diabetes in our state and throughout the world.     

Age at onset and long-term metabolic control affect height in type-1 diabetes mellitus

Reduced height as a consequence of type-I-diabetes mellitus in childhood has been reported in many studies. However, it is still debated whether good metabolic control can normalize the growth rate. A total of 436 children (204 boys, 232 girls, mean age at diagnosis of diabetes 8.2+/-0.2 years) were followed at our outpatient diabetes centre. Z-scores for height were evaluated in relation to duration of diabetes, age at onset and long-term metabolic control. At diagnosis, height in children with diabetes was significantly above the reference population (+0.43+/-0.09). Standardized height decreased during the subsequent course of diabetes. This likely represents a delay of growth, as the final height (chronological age > 18 years, n = 144) was +0.27+/-0.09. Growth reduction was more pronounced in patients diagnosed before the onset of puberty and final height in patients with a prepubertal onset of diabetes was significantly lower (+0.10+/-0.13) compared to patients with a pubertal/postpubertal onset (+0.52+/-0.14). Among patients with a prepubertal onset, the subgroup with "poor" metabolic control (long-term median HbA(Ic) >7%) lost significantly more height compared to patients with "good" metabolic control. CONCLUSION: Despite modern treatment regimens, reduced longitudinal growth can still be demonstrated in type-I diabetes. This parameter therefore provides a valuable endpoint for quality control in paediatric diabetology.     

The HLA system and diabetes mellitus

There is a significant positive association between insulin dependent diabetes, irrespective of age of onset, and the HLA system, whereas there is no association of HLA antigens with non-insulin dependent diabetes. There is a significant concordance value for HLA antigen frequencies in insulin dependent diabetics from three different centres, indicating that the genes (s) conferring susceptibility to this type of diabetes is possibly present in all "juvenile-onset" diabetics and is in linkage disequilibrium with all the B locus alleles.     

Renal structural-functional relationships in early diabetes mellitus

To define the earliest renal morphological changes in patients with type I diabetes, we studied renal function and morphometric analysis of renal biopsies in 59 patients with diabetes for 5-12 years and normal blood pressure, normal creatinine clearance (CCr), and negative dipstick urinary protein. Arteriolar hyalinization and intimal fibrous thickening were noted in 43%. Glomerular basement membrane thickness and fractional mesangial volume were increased in 51% and 56%, respectively. The pre-pubertal and post-pubertal years of diabetes were associated with similar degrees of renal structural changes, but during the pre-pubertal years normal urinary albumin excretion (UAE) was seen. Principal factor analysis of morphometric structural parameters yielded four clusters of variables: "glomerular size" correlated with patient age, CCr, and UAE; "peripheral capillary decrease" correlated with glycosylated hemoglobin, diastolic blood pressure, glomerular filtration rate, and UAE; "mesangial increase" correlated with UAE; and "interstitial scarring" correlated with diastolic blood pressure. This study provides unique documentation of renal structural abnormalities which precede clinically evident renal functional abnormalities and documents that these early structural abnormalities are present in the pre-pubertal years of diabetes as well as postpuberty, and are associated with each other in constellations that correspond to postulated mechanisms in diabetic nephropathy.     

Effects of changing diagnostic criteria on the risk of developing diabetes

OBJECTIVE: The American Diabetes Association (ADA) has recommended that the fasting plasma glucose (FPG) level used to diagnose diabetes be changed from 7.8 mmol/l (the level recommended by the National Diabetes Data Group [NDDG] in 1979) to 7.0 mmol/l. We examined the impact of this change on rates of progression to overt diabetes from different levels of FPG. RESEARCH DESIGN AND METHODS: Using the laboratory database of Mayo Clinic, we assembled a cohort of 8,098 nondiabetic Olmsted County residents 40 years of age or older on 1 July 1983. Subjects were followed for a median of 9 years. RESULTS: Among 7,567 individuals with follow-up FPG data, 778 (10.3%) progressed to ADA diabetes and 513 (6.8%; P < 0.0001) progressed to NDDG diabetes. The risk of developing ADA diabetes was 7, 19, and 39% for individuals with initial FPG values in the ranges of <5.6, 5.6-6.0, and 6.1-6.9 mmol/l, respectively. For progression to NDDG diabetes, the respective risks were 3, 11, and 25%. A clear gradient of risk was observed within the "normal" range of FPG (<5.6 mmol/l). Among the 793 individuals who developed ADA diabetes, 222 (29%) developed NDDG diabetes simultaneously and 291 (37%) developed NDDG diabetes later. In all FPG subgroups, progression to ADA diabetes occurred approximately 7 years sooner than progression to NDDG diabetes. CONCLUSIONS: The baseline level of FPG is a major predictor of an individual's risk of developing diabetes. The proposed change in the diagnostic criteria for diabetes will lead to earlier diagnosis among individuals who are destined to develop the disease.     

The role of urine sugar in diabetic management

The concentration of reducing sugar in the urine is commonly used in the management of diabetes in children. Supplemental doses of regular insulin are administered in response to the concentration of urine sugar according to a protocol termed the "sliding scale." This practice assumes that the concentration of sugar in urine is a good indicator of the plasma glucose concentration. This assumption was tested by comparing urine sugar concentrations in first and second voided urines with the plasma glucose concentrations in 220 children with diabetes. The correlation was good (r = .92) for both the first and second voided urine specimens. Thus, urine sugar concentrations in general define the level of plasma glucose. The large standard deviation of the plasma glucose at each concentration of urine sugar, however, limits the usefulness of urine sugar as an accurate reflection of the coincident plasma glucose concentration. The urine sugar concentration, although useful for the general management of diabetes, provides significant risk when used to guide frequent adjustments in insulin administration. Therefore, the "sliding scale" should not be used in the treatment of children with diabetes.     

Coronary atherosclerosis or diabetic cardiomyopathy? Pathoanatomic changes of blood vessels, nerves and myocardium in patients with diabetes mellitus

In patients with diabetes mellitus, heart disease is more common that in the background populations and has a more serious prognosis. The reasons are only partially understood. Whether patients with diabetes mellitus have a more diffuse and pronounced coronary atherosclerosis has been the subject of many investigations with diverging results. However, the larger studies suggest that coronary atherosclerosis is more pronounced and diffuse in diabetics compared with non-diabetic patients. The pathoanatomic picture of the atherosclerotic process seems to be identical in patients with and without diabetes mellitus. A number of structural abnormalities in the intramural vessels and interstitial tissue of the heart have been demonstrated in diabetics. However, similar abnormalities have also been reported in non-diabetic patients. With respect to where "diabetic cardiomyopathy" is a specific entity, the existing data are not confirmative. Whether diabetes mellitus per se induces functional changes in the coronary vascular system leading to myocardial ischaemia and dysfunction is a subject for future investigations.     

Health beliefs and folk models of diabetes in British Bangladeshis: a qualitative study

OBJECTIVE: To explore the experience of diabetes in British Bangladeshis, since successful management of diabetes requires attention not just to observable behaviour but to the underlying attitudes and belief systems which drive that behaviour. DESIGN: Qualitative study of subjects' experience of diabetes using narratives, semi-structured interviews, focus groups, and pile sorting exercises. A new qualitative method, the structured vignette, was developed for validating researchers' understanding of primary level culture. SUBJECTS: 40 British Bangladeshi patients with diabetes, and 10 non-Bangladeshi controls, recruited from primary care. RESULT: Several constructs were detected in relation to body image, cause and nature of diabetes, food classification, and knowledge of complications. In some areas, the similarities between Bangladeshi and non-Bangladeshi subjects were as striking as their differences. There was little evidence of a fatalistic or deterministic attitude to prognosis, and most informants seemed highly motivated to alter their diet and comply with treatment. Structural and material barriers to behaviour change were at least as important as "cultural" ones. CONCLUSION: Bangladeshi culture is neither seamless nor static, but some widely held beliefs and behaviours have been identified. Some of these have a potentially beneficial effect on health and should be used as the starting point for culturally sensitive diabetes education.     

Some current aspects of environmental fluoride

This review presents a Total Environment evaluation of current inorganic fluoride intake by human populations. Inorganic fluoride is a persistant bioaccumulator, and the ever-increasing use (and release) of fluoride compounds in the environment should be of long-term concern in population sub-groups who are most susceptible, and therefore, most "at risk". One of these sub-groups consists of people with impaired kidney function, including subjects with nephorphatic diabetes. The diabetes factor is of particular relevance, not only because the incidence of diabetes has increased by 6%/yr during the period 1965-1975, but also because subjects with nephropathic diabetes can exhibit a polydipsia-polyurea syndrome that results in increased intake of fluoride, along with greater-than-normal retention of a given fluoride dosage. People with inadequate dietary intakes (particularly of Ca and/or Vitamin C) are also likely to be more "at risk" as a consequence of low-dose long-term fluoride ingestion. Evidence is presented, showing that there has been an escalation in dialy fluoride intake via the total human food-and-beverage chain, with the likelihood that this escalation will continue in the future. Recent observations, relating to an increasing incidence of chronic fluoride intoxication among humans, is also emphasized.     

Energy substrate metabolism during stress

Energy substrate metabolism during stress is characterized by increased REE (resting energy expenditure), hyperglycemia, hyperlactatemia and protein catabolism. This stress-induced hypermetabolic responses are closely related to increased secretion of neurohormonal and cytokine mediators. The insulin resistance hyperglycemia has been called "stress diabetes" or "surgical diabetes". Glucose disposal has been thought to be impaired in this condition. However, glucose uptake in most tissue is non-insulin mediated. Recent studies showed glucose uptake elevated in sepsis or TNF infusion. Insulin-regulatable glucose transporter (GLUT4) is present only in muscle, heart and adipose tissues. It was demonstrated that insulin binding to membrane receptors in these tissues was intact. This hyperglycemia in stress diabetes results from a postreceptor mechanism. Stress hyperlactatemia is thought to be caused by decreased pyruvate dehydrogenase activity rather than tissue hypoperfusion. Hyperlactatemia may promote gluconeogenesis. Glucose is a essential energy substrate in some tissues such as brain, erythrocyte and leukocyte. Hyperglycemia may be viewed as a beneficial response during stress.     

Diabetic retinopathy

Retinal complications of diabetes mellitus are chronic but late functional signs can lead to delayed diagnosis and treatments. Light coagulation (argon laser radiation) is recognized for its efficiency at the stage of "mature" retinopathy, converting the prognosis of a disease which was leading to blindness. Photocoagulation is not used in the early stages (early or strictly posterior pole diabetic retinopathy); partial regression or stabilization can be hoped with intensive medical treatment of diabetes. Treatment of diabetes could become the best preventive treatment. Light coagulation is used at stages when the disease is not reversible (non or preproliferative and proliferative). In tractional retinal detachment surgery remains active, always corresponding to too late treatments. Although pharmacology has progressed (inhibitors of platelet agregation and of non enzymatic glycation) medical therapy remains controversial.     

Verapamil-induced "primary" polydipsia

An 11-month-old male infant with recurrent supraventricular tachycardia (SVT) was treated with oral verapamil. Shortly thereafter he developed marked changes in behavior including lethargy, intensely increased thirst and urination, and irritability when denied fluids. "Primary" polydipsia was diagnosed following an evaluation which showed no evidence of adrenal insufficiency, diabetes insipidus, diabetes mellitus, hypercalcemia, hyperosmolality, or renal disease. The symptoms resolved 1 week after verapamil was discontinued.     

The contribution of "cure by dapsone monotherapy'' to the reduction of prevalence of leprosy in the State of Orissa, India, 1983-1993

The activity of phosphofructokinase-2, fructose, 1,6-bisphosphatase, glucokinase, and also the level of fructose 2,6-bisphosphate and glycogen were examined in the liver of normal, and streptozotocin-diabetic rats. It was shown that the activity of phosphofructokinase-2 was decreased in the liver of diabetic rats. Besides that the activity determined at pH 6.6 (the "active" or unphosphorylated enzyme form) was 3-fold reduced whereas the "total" enzyme activity as measured at pH 8.5 was lowered 1,7-fold. The phosphofructokinase-2 activity assay at two pH values allows to estimate a degree of phosphorylation of bifunctional enzyme which is markedly enhanced in diabetes. The fall of the bifunctional enzyme k in case activity is accompanied by the lowered fructose 2.6-bisphosphate level, increased fructose 1,6-bisphosphatase activity that in turn favours the liver tissue glycolysis inhibition and gluconeogenesis enhanced in diabetes.     

Pathophysiologic mechanisms of early changes in renal hemodynamics in diabetes mellitus

The early stages of diabetes mellitus are in some patients associated with renal haemodynamic changes resulting in increased glomerular filtration. This "diabetic hyperfiltration" is considered to be one of pathophysiological mechanisms and risk factors for the development of diabetic nephropathy. The aim of this paper is to review some contemporary views on pathophysiological mechanisms leading to this disorder with emphasis on the role impaired activity of humoral factors influencing renal haemodynamics. In addition to poor metabolic control due to insulinopenia there is a convincing experimental evidence suggesting the role of atrial natriuretic factor and endothelium-derived nitric oxide in mediating renal haemodynamic changes in diabetes. Enhanced renal activity of angiotensin I converting enzyme resulting in local overproduction of angiotensin II and accelerated degradation of kinins may be another factor contributing to the genesis of diabetic hyperfiltration. Hyperglycaemia induces changes in cellular signalling of these vasoactive systems. Furthermore, diabetes is a state of decreased capability of renal vascular bed to autoregulate blood flow likely due to altered activity of tubuloglomerular feedback and ion channels.     

Internet-based diabetes self-management and support: Initial outcomes from the Diabetes Network project.

Objective: The Diabetes Network (D-Net), a randomized trial of an Internet-based, diabetes self-management and peer support intervention, was evaluated after 3 months. Design: The study assessed separate and combined effects of diabetes self-management and peer support. Outcomes included physiologic, behavioral, mental health, and website usage. Results are presented on the first 160 type 2 diabetes patients recruited from 16 primary care offices. Of those eligible, 61 % participated in the study. Results: There was significant overall improvement, especially on dietary behavior, but no significant between-condition differences. Conclusions: Providing basic diabetes information as well as a "personal coach," self-management intervention entirely over the Internet proved feasible. Even novice computers users will participate in an Internet-based program to assist themselves in managing their diabetes. Validated Internet interventions could prove to be valuable resources that overcome many costs and limitations of conventional diabetes management. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contents of glycogen in neutrophils in patients with diabetes]

Glycogen neutrophils level was evaluated in 54 patients with non-insulin dependent diabetes mellitus (NIDDM) and 10 patients with insulin dependent diabetes mellitus (IDDM). Glycogen concentration estimated by histochemical method was lower in diabetics than in control group. Patients with NIDDM were divided in the groups according to: sex, duration of disease, a kind of complications and a way of treatment. The glycogen contents in neutrophils, defined in "score"-unit was not different in isolated groups. There was found significant correlation between glycogen contents in neutrophils and the metabolic control in patients with IDDM (r = 0.72) and less significant in patients with NIDDM (r = 0.29).     

Intervention in autoimmune diabetes by targeting the gut immune system

BB rats and nonobese diabetic (NOD) mice spontaneously develop autoimmune insulin dependent diabetes and serve as models for human type I diabetes. During progression of the disease the cytokine pattern elaborated by islet infiltrating immune cells shifts from a Th2 or Th0 toward Th1 type. Only the latter is associated with "destructive" insulitis. We discuss here attempts to modulate disease progression by targeting the gut immune system with bacterial immunostimulants. Oral dosing of diabetes prone BB rats with lipopolysaccharide (LPS) or the Escherichia coli extract OM-89 lead to a Th2-shift of pancreatic mRNA expression. In vitro studies showed that repeated exposure toward LPS or OM-89 lead to downregulation of proinflammatory macrophage responses. In the NOD mouse, repeated oral dosing of OM-89 caused a Th2 shift in the gut cytokine gene expression, probably because of desensitization of macrophages and other antigen presenting cells. Concomitantly, diabetes prevention by oral insulin was improved. In conclusion, oral dosing with bacterial immunostimulants dampens Th1 type immune reactivities of the gut immune system and thereby promotes oral tolerance mechanisms. Downregulation of proinflammatory immune reactivities by repeated exposure to bacterial stimulants requires intact desensitization mechanisms in macrophages or other antigen presenting cells.     

Radioimmunoassay for glutamic acid decarboxylase (GAD65) autoantibodies as a diagnostic aid for stiff-man syndrome and a correlate of susceptibility to type 1 diabetes mellitus

OBJECTIVE: To establish and validate a double-antibody radioimmunoassay (RIA) for detecting serum auto-antibodies against glutamic acid decarboxylase (GAD65). This enzyme catalyzes synthesis of the neurotransmitter gamma-aminobutyric acid in neurons and pancreatic islet cells. MATERIAL AND METHODS: We compared the frequency of GAD65 and other "thyrogastric" autoantibodies in adult patients with stiff-man (Moersch-Woltman) syndrome, type 1 diabetes, or polyendocrine disorders and in healthy subjects. The frequency of pancreatic islet cell antibody (ICA) detection was also assessed. The GAD65 RIA was validated by testing blinded samples, by confirming the specificity of low-titered positive results by "cold" antigen inhibition, and by comparing the RIA results with results of a kit assay incorporating staphylococcal protein A as immunoprecipitant. Recombinant GAD65 protein labeled with 125I was used as antigen, and a combination of anti-human IgG and IgM was used as immunoprecipitant. Seropositivity was determined for ICA and gastric parietal cell antibodies by indirect immunofluorescence assays and for thyroid peroxidase (microsome) and thyroglobulin antibodies by agglutination assays. RESULTS: We detected GAD65-specific antibodies in all but 1 of 46 local patients with stiff-man syndrome (98%); 16 had evidence of diabetes. Positive values exceeded 20 nmol/L in 96%, and 89% were ICA-positive; 76% had additional thyrogastric antibodies. Of 41 patients with type 1 diabetes (17 local and 24 workshop serum specimens), 33 were GAD65 antibody-positive (80%); 85% of these positive values were 20 nmol/L or lower. Only 18% of sera from patients with type 1 diabetes were ICA-positive, but 59% had other thyrogastric autoantibodies. Of 20 patients with autoimmune endocrinopathies without diabetes or stiff-man syndrome, 35% were GAD65 antibody-positive, 5% were ICA-positive, and 90% were thyrogastric antibody-positive. Of 117 healthy control subjects, 8% were GAD65 antibody-positive, and a third of those had other thyrogastric antibodies (14% overall); none was ICA-positive. CONCLUSION: Seropositivity in the double-antibody RIA for GAD65 autoantibody is a sensitive and specific marker of predisposition to type 1 diabetes and related organ-specific autoimmune disorders. As such, this RIA is complemented by assays for thyroid and gastric parietal cell autoantibodies.