Treatment of asymptomatic diabetes mellitus

A large number of individuals currently diagnosed as having diabetes mellitus are asymptomatic. In order to provide rational therapy for this patient population, it is necessary to focus upon the differences between these patients and the classic prototypes with polyuria and weight loss, who require insulin for survival. Patients with asymptomatic diabetes do not need insulin for survival, and, by definition, they do not need it to alleviate symptoms. They tend to be middle-aged and overweight, but they can be young and thin. Their degree of hyperglycemia is moderate, often indistinguishable from that of normal individuals in their day-to-day existence. Indeed, they can often be differentiated from normal persons only on the basis of their blood glucose response to the stress of a large dextrose challenge; in this regard, the potential problem of over-diagnosing diabetes has been discussed. Since the major problem facing patients with asymptomatic diabetes is accelerated atherogenesis, the therapeutic approach must be based upon efforts to delay or prevent the onset of vascular disease. It has yet to be shown that any therapeutic intervention helps such patients, but an argument has been made in support of the following goals in subjects with asymptomatic diabetes whose fasting blood glucose level is less than 170 mg/100 ml: (1) stop smoking, (2) control hypertension, (3) attain ideal body weight, and (4) maintain blood triglyceride and cholesterol levels well within normal limits. Attempts to lower blood glucose with either insulin or oral agents do not seem indicated in the majority of patients within this defined diabetic population.     

Treatment of hypertension associated with diabetes mellitus

The number of patients with non-insulin-dependent-diabetes mellitus (NIDDM) is dramatically increasing in Japan and estimated to be 6 million, more than one of ten adults. It is well known that more than a half of diabetics are hypertensive. Therefore, it is very important to treat hypertension to reduce cardiovascular events as well as end-stage renal disease. At first, life style modification such as body weight reduction, exercise and restriction of salt and alcohol intake will be recommended. Improved glycemic control by such a non-pharmacological therapy will lower blood pressure. Recent studies demonstrated that hypoglycemic agents improving insulin resistance such as metformin and troglitazone reduce blood pressure. If these maneuvers do not lower blood pressure, hypotensive medication will be necessary. As a first line therapy, ACE inhibitor, alpha 1-blocker or Ca-channel blocker will be selected. In diabetics with proteinuria or micro-albuminuria, ACE inhibitors will be effective to delay the progression of diabetic nephropathy.     

Treatment of diabetes mellitus with long-acting biguanides

The paper discusses of the results of treatment with preparations of phenylethylbiguanide (dibotin, meltrol, dipar, dibophen-retard), of butylbiguanide (silubin-retard, buforming-retard) and of dimethyl-biguanide (glucophage-retard). All these preparations were of prolonged action. The treatment was carried out in 242 patients. The saccharolytic action of the active agent contained in one tablet of each type of biguanide was approximately the same. Biguanides of prolonged action were highly effective in obese patients with diabetes mellitus of moderate severity. The best results were obtained in complex treatment with biguanides of prolonged action together with sulfonylurea preparations of the second generation. There were noted almost no toxic reactions from the use of biguanides up to 2 tablets a day.     

Platelet-leukocyte-cross-talk in diabetes mellitus

The physiological meaning of platelets has been best documented for acute coronary syndromes where platelets act as "first responsive elements" triggering the final occlusive thrombus after plaque rupture has occurred. This situation is particularly relevant for patients with NIDDM-type diabetes regularly showing complicated plaque architecture. Predictive power for acute ischemic events e.g. following angioplasty has been proven, and this has dominated the attention exclusively towards the hemostatic function of platelets. Meanwhile, a variety of particularly important platelet features have been identified: a) promotion of liquid phase coagulation; b) regulation of the local vascular tone; c) active modulation of tissue modeling at lesion sites; d) adhesion molecule-mediated communication with a variety of corpuscular blood (and non-blood cells). With emerging recognition of the latter role, the pathophysiological scope of platelets exceeds the well-established role as microemboli, local atherosclerosis amplifiers and triggers of gross thrombosis. In diabetes mellitus of either type, increased populations of circulating platelets have been identified expressing activation dependent adhesion molecules such as activated alpha 2 beta 3 (GPIIbIIIa), lysosomal GP53, thrombospondin or, perhaps most importantly "P-selectin" (CD62 p). This suggests that these adhesion molecules among others can also mediate platelet-leukocyte interactions potentially resulting in inflammatory tissue damaging processes in addition to the immanent tendency towards (micro-)thrombosis. This review works out a more general view on the meaning of platelet activation beyond hemostaseology and updates the actual knowledge of platelet-leukocyte communication checkpoints with particular reference to the diabetic state outlining new pharmacological concepts for intervention.     

Gestational diabetes mellitus and subsequent development of overt diabetes mellitus

GDM develops in 1-3% of all pregnancies. Women with GDM are characterized by a relatively diminished insulin secretion coupled with a pregnancy-induced insulin resistance primary located in skeletal muscle tissue. The cellular background for this insulin resistance is not known. The binding of insulin to its receptor and the subsequent activation of the insulin receptor tyrosine kinase have significant importance for the cellular effect of insulin. Thus, the pathogenesis to the insulin resistance was studied by investigating insulin receptor binding and tyrosine kinase activity in skeletal muscle biopsies from women with GDM and pregnant controls. No major abnormalities were found in GDM wherefore it is likely that the insulin resistance is caused by intracellular defects distal to the activation of the tyrosine kinase. Glucose tolerance returns to normal postpartum in the majority of women with GDM. However, previous studies, in populations quite different from a Danish population, have shown that women with previous GDM have a high risk of developing overt diabetes mellitus later in life. Hence, we aimed to investigate the prognosis of women with previous GDM with respect to subsequent development of diabetes and also to identify predictive factors for the development of overt diabets in these women. A follow-up study of diet treated GDM women diagnosed during 1978 to 1985 at the Rigshospital, Copenhagen was performed. Glucose tolerance was evaluated in 241 women (81% of the GDM population) 2-11 years after pregnancy. Abnormal glucose tolerance was found in 34.4% of the women (3.7% IDDM, 13.7% NIDDM, 17% IGT) in contrast to a control group where none had diabetes and 5.3% had IGT. Logistic regression analysis identified the following independent risk factors for later development of diabetes: a high fasting glucose level at diagnosis of GDM, a delivery more than 3 weeks before term, and an abnormal OGTT 2 months postpartum. Low insulin secretion at diagnosis of GDM was also an independent risk factor. The presence of ICA and GAD-autoantibodies in pregnancy was associated with later development of IDDM. In another study the following techniques: hyperinsulinaemic euglycaemic clamp, indirect calorimetry and tritiated glucose infusion were used to evaluate insulin sensitivity in glucose tolerant nonobese women with previous GDM and controls. A decreased insulin sensitivity due to a decreased non-oxidative glucose metabolism in skeletal muscle was found in women with previous GDM. Hence, the activity of three key enzymes in intracellular glucose metabolism (GS, HK and PFK) was studied in skeletal muscle biopsies obtained in the basal state and after 3 h hyperinsulinaemia, with the aim to identify the cellular defects causing the decreased insulin sensitivity. However, no abnormalities in enzyme activity was found. The same group of previous GDM women had a relatively reduced insulin secretion evaluated by the IVGTT. A longitudinal study of 91 GDM women showed a relatively reduced insulin secretion to oral glucose in pregnancy, postpartum as well as 5-11 years later. Thus the present review has shown that even nonobese glucose tolerant women with previous GDM are characterized by the metabolic profile of NIDDM i.e. insulin resistance and impaired insulin secretion. Hence, the combination of this finding together with the significantly increased risk for development of diabetes indicates that all women with previous GDM should have a regular assessment of their glucose tolerance in the years after pregnancy. The first OGTT should be performed around 2 months postpartum in order to diagnose women already diabetic and to identify women with the highest risk for later development of overt diabetes. Women with previous GDM comprise a target group for future intervention trials with the aim to prevent or delay development of NIDDM and IDDM.     

Juvenile diabetes mellitus

Each year members of a different medical faculty prepare articles for "Practical Therapeutics." This is the seventh in a series from the University of Texas Medical School at Houston.     

Uroradiology of diabetes mellitus

Diabetes mellitus is a prevalent disorder, well controlled in many persons with prolongation of life. Several radiologic manifestations are sufficiently specific to suggest a diagnosis in the unidentified patient, but even more important is an awareness of the sometimes life-threatening complications of diabetes which can be diagnosed from uroradiologic studies. We review the following urinary tract manifestations and complications of diabetes: pyelonephritis, perinephric abscess, renal papillary necrosis, emphysematous pyelonephritis, emphysematous cystitis, fungus infections, calcification of the vas deferens, seminal vesicle, and intrarenal branches of the renal artery, neuropathic bladder, and renal failure.     

Heart disease in diabetes mellitus

The spectrum of heart disease in diabetic patients is broad and complex. This article discusses the epidemiologic associations between the two causes. It attempts to summarize the effects of diabetes at the cellular, vascular, and myocardial levels. The clinical manifestations are explored, and the treatment of heart disease as it pertains to diabetic patients is discussed.     

The cornea in diabetes mellitus

Diabetes mellitus has a significant effect on morphological, metabolic, physiological, and clinical aspects of the cornea. Morphological changes are manifest in the corneal epithelium, epithelial basement membrane and basement membrane complexes, stroma, and endothelium. The homeostasis of these structures can be altered by diabetes in both the non-stressed and the stressed cornea, causing myriad primary and postoperative manifestations. The polyol pathway appears to be involved in some of the pathophysiology mechanisms leading to these clinical entities and appears also to play a role in the treatment of some diabetic pathological processes associated with diabetes mellitus.     

Evoked potentials in diabetes mellitus

A comparison was made between 44 humeral fractures treated conservatively with functional bracing (Group 1) and 45 treated by operation with a locking nail (Group 2). Thirty-eight of the 44 patients in Group 1 (86%) and 22 of the 45 patients in Group 2 (47%) regained full movement of the shoulder joint. The functional end results were somewhat better in Group 1 although over 90% of patients in both groups were able to clasp their fingers behind their necks and to reach up their backs without restriction. Two patients developed a pseudarthrosis in Group 1, and 2 patients in Group 2 required operative revision due to a haematoma in 1 case and as a result of an infection in the other. There were 6 cases of primary radial nerve damage in both groups, and 6 had to be decompressed operatively. Residual sensory and motor disturbance remained in 2 patients in Group 1. Both methods are useful for the treatment of humeral shaft fractures. We advocate functional bracing as the method of choice if no contraindications exist.