How far should blood pressure be reduced in diabetic hypertensive patients?

EPIDEMIOLOGY OF DIABETES: Diabetes mellitus and arterial hypertension are closely related diseases that strongly predispose an individual to atherosclerotic cardiovascular disease and to renal failure. High blood pressure is twice as frequent in diabetics compared with the general population, and often precedes and contributes to the development of diabetic nephropathy. The prevalence of coexisting arterial hypertension and non-insulin-dependent diabetes mellitus (NIDDM) is increasing as populations age, giving an increased prevalence of both diseases. TREATMENT OF HYPERTENSIVE DIABETIC PATIENTS: The goal of treating arterial hypertension in diabetic patients is to prevent death and disability associated with high blood pressure. In addition, other reversible risk factors for cardiovascular disease, seen so frequently in hypertensive diabetics, also need to be addressed. The optimal goal of blood pressure control in diabetics has not been established, but there are indications that it should be lower than the 130/85 mmHg systolic/diastolic pressure recommended by current guidelines. In the presence of multiple associated risk factors, most guidelines suggest a threshold for intervention of > or = 140/90 mmHg. In particular, in hypertensive diabetic patients intervention must be early and aggressive.     

Diabetic nephropathy

Diabetic nephropathy accounts for almost a third of all causes of ESRD. Microalbuminuria screening among diabetics can offer early detection of incipient nephropathy. Aggressive treatment with ACE inhibitors may delay the onset of overt renal failure or delay its progression. Furthermore, intensive control of blood glucose has also been proven to prevent the microvascular complications of diabetes and should be pursued in both IDDM and NIDDM. The high association of diabetes mellitus with hypertension presents another problem to the clinician. It is necessary to control blood pressure to prevent further progression of renal failure. The choice of antihypertensive medications, however, becomes a therapeutic dilemma because of the metabolic and lipid disturbances that some drugs can cause. ACE inhibitors, CCBs, alpha-agonists, and low-dose diuretics, alone or in combination, may be tried to normalize blood pressures. Although beta-blockers are widely used and effective in nondiabetics, these agents should be considered the drugs of last resort because of their adverse effects, which are particularly troublesome for diabetics. Moderate protein restriction should also be advocated as a helpful adjunct to therapy.     

Effects of locus coeruleus stimulation on the responses of SI neurons of the rat to controlled natural and electrical stimulation of the skin

Recent epidemiologic data demonstrate a dramatic increase in the incidence of end-stage renal disease (ESRD) in patients with non-insulin-dependent diabetes mellitus (NIDDM), thus dispelling the mistaken belief that renal prognosis is benign in NIDDM. Currently, the leading cause of ESRD in the United States, Japan, and in most industrialized Europe is NIDDM, accounting for nearly 90% of all cases of diabetes. In addition to profound economic costs, patients with NIDDM and diabetic nephropathy have a dramatically increased morbidity and premature mortality. NIDDM-related nephropathy varies widely among racial and ethnic groups, genders and lifestyles; and gender may interact with race to affect the disease progression. While the course of insulin-dependent diabetes mellitus (IDDM) progresses through well-defined stages, the natural history of NIDDM is less well characterized. NIDDM patients with coronary heart disease have a higher urinary albumin excretion rate at the time of diagnosis and follow-up. This greater risk may also be associated with hypertension and hyperlipidemia, and genes involved in blood pressure are obvious candidate genes for diabetic nephropathy. Hyperglycemia appears to be an important factor in the development of proteinuria in NIDDM, but its role and the influence of diet are not yet clear. Tobacco smoking can also be deleterious to the diabetic patient, and is also associated with disease progression. Maintaining euglycemia, stopping smoking and controlling blood pressure may prevent or slow the progression of NIDDM-related nephropathy and reduce extrarenal injury. Treatment recommendations include early screening for hyperlipidemia, appropriate exercise and a healthy diet. Cornerstones of management should also include: (1) educating the medical community and more widely disseminating data supporting the value of early treatment of microalbuminuria; (2) developing a comprehensive, multidisciplinary team approach that involves physicians, nurses, diabetes educators and behavioral therapists; and (3) intensifying research in this field.     

Benefits and cost of antihypertensive treatment in incipient and overt diabetic nephropathy

PREVALENCE: The prevalence of abnormally elevated urinary albumin excretion rate (> 30 mg/24 h) is approximately 40% in insulin-dependent and in non-insulin-dependent diabetic patients. Diabetes has become the leading cause of end-stage renal failure in Europe, USA and Japan. Approximately 90% of the direct and indirect costs of caring for diabetic patients are spent on the complications of diabetes. RISK FACTORS: Identification of patients at high risk of developing diabetic nephropathy is possible by screening for microalbuminuria (30-300 mg/24 h). Additional risk factors/ markers for development of nephropathy are male sex, genetic predisposition, ethnic conditions, early onset of diabetes, poor metabolic control, hyperfiltration, elevated prorenin and smoking. Elevated urinary albumin excretion rate indicates a substantially increased cardiovascular morbidity and mortality risk in diabetic patients. PREVENTION OF NEPHROPATHY: Randomized controlled trials in normotensive insulin-dependent and in non-insulin-dependent diabetic patients with persistent microalbuminuria indicate that angiotensin converting enzyme (ACE) inhibitors diminish urinary albumin excretion rate, and postpone and may even prevent progression to clinical overt nephropathy. These findings indicate that screening and intervention programs could probably save lives and lead to considerable economic savings. TREATMENT OF NEPHROPATHY: Systemic blood pressure elevation to a hypertensive level is an early and frequent phenomenon in diabetic nephropathy. Furthermore, nocturnal blood pressure elevation (non-dippers) occurs more frequently in patients with nephropathy. Systemic blood pressure elevation, hyperglycaemia, albuminuria and the D polymorphism in the ACE gene accelerate the progression of diabetic nephropathy. Studies of the impact of other potential progression promoters (i.e. smoking, hyperlipidaemia and protein intake) have yielded conflicting results. Effective blood pressure reduction using ACE inhibitors or drugs of other classes, or both, frequently in combination with diuretics reduces albuminuria, delays the progression of nephropathy, postpones renal failure and improves survival in patients with diabetic nephropathy. Antihypertensive treatment for diabetic nephropathy extends life and saves money.     

Diabetes and hypertension: the bad companions

DIABETES AND HYPERTENSION: Diabetes mellitus and hypertension are interrelated diseases that strongly predispose people to atherosclerotic cardiovascular disease. Hypertension is about twice as frequent in individuals with diabetes as in those without. The prevalence of coexisting hypertension and diabetes appears to be increasing in industrialized nations because populations are aging, and both hypertension and non-insulin-dependent diabetes mellitus (NIDDM) increase with age. An estimated 35-75% of diabetic cardiovascular and renal complications can be attributed to hypertension. ESSENTIAL HYPERTENSION: Essential hypertension accounts for the majority of hypertension in individuals with diabetes, particularly those with NIDDM, who constitute over 90% of those with a dual diagnosis of diabetes and hypertension. Diabetic nephropathy, which occurs after 15 years of diabetes in one-third of those with insulin-dependent diabetes and 20% of those with NIDDM, is an important contributing factor to the development of hypertension in the diabetic. New investigations should focus increasingly on identifying appropriate antihypertensive agents that not only lower blood pressure but also reduce cardiovascular risk and retard the rate of progression of diabetic renal disease.     

Effects of the herbicide atrazine on Ambystoma tigrinum metamorphosis: duration, larval growth, and hormonal response

Microalbuminuria is not only a predictor of diabetic nephropathy in type 1 diabetes, but also a potent marker of cardiovascular risk, especially in type 2 diabetes. Microalbuminuria also predicts cardiovascular morbidity in the general population. We describe semi-quantitative and quantitative methods for determination of low urinary excretion of albumin. Pathogenetic hypotheses common to both renal and endothelial dysfunction are discussed, suggesting that microalbuminuria may be a link between micro- and macroangiopathy. Improved glycemic control and antihypertensive treatment postpone and potentially prevent development of nephropathy in diabetic patients with microalbuminuria. These interventions must be instituted early in the development of diabetic nephropathy. In type 2 diabetes, prospective studies are needed to evaluate the precise impact of such a therapy on the cardiovascular risk.     

Diabetic nephropathy. Its relationship to hypertension and means of pharmacological intervention

Hypertension and diabetes mellitus are common chronic conditions which frequently coexist. Diabetic nephropathy is a major cause of elevated blood pressure in patients with insulin-dependent diabetes mellitus (IDDM). Diabetic nephropathy, arterial sclerosis, obesity and association of essential hypertension can be the causes of hypertension in patients with non-insulin-dependent diabetes mellitus (NIDDM). Ambulatory blood pressure monitoring has revealed that the nocturnal fall of blood pressure is blunted in patients with diabetic nephropathy. A blunted diurnal blood pressure variation is seen in microalbuminuric diabetic patients and even in some normoalbuminuric patients. Accumulating data suggest that normalisation of blood pressure in hypertensive IDDM patients is most important to minimise the loss of kidney function. Angiotensin converting enzyme (ACE) inhibitors have been reported to be effective in postponing the development of nephropathy and in slowing its progression. Whether only ACE inhibitors have such beneficial renal effects on diabetic nephropathy is under discussion. While many studies have suggested that insulin resistance and hyperinsulinaemia are related to an elevated blood pressure in hypertensive patients, there does not seem to be enough evidence to prove that insulin per se can raise blood pressure in humans. Neither an insulin infusion within a physiological range nor sustained hyperinsulinaemia and insulin resistance (e.g. patients with insulinoma, cystic ovary syndrome) have been associated with an elevated blood pressure. Insulin resistance in some hypertensive patients may be a consequence of a decreased blood flow due to an increased peripheral resistance. Preliminary evidence suggests that low birth weight or impaired fetal growth is related to hypertension and NIDDM. Familial clustering of diabetic nephropathy suggests the contribution of genetic susceptibility and/or environmental inheritance. The frequent association of nephropathy with hypertension has led to research on the genes related to hypertension (ACE, angiotensinogen). Nevertheless, to date no reliable and clinically useful genetic marker has been found. Attempts to correct the metabolic abnormalities derived from diabetes are a new topic in the treatment of diabetic nephropathy. The effects of HMG CoA reductase inhibitors (antihypercholesterolaemic drugs), aldose reductase inhibitors (inhibitors of the polyol pathway) and glycation inhibitors (inhibitors of formation of advanced glycosylation end-products) on diabetic nephropathy have been evaluated in animal studies and in some clinical trials. Thus far, results with HMG CoA reductase and aldose reductase inhibitors have been somewhat conflicting. The potential therapeutic role of glycation inhibition in the treatment of diabetes deserves further study.     

Costs of intensive insulin therapy in type 1 diabetes mellitus. Experiences from the DCCT study

Diabetes mellitus is one of the most common metabolic diseases in many countries of the world. Its prevalence in Germany has increased 7- to 8-fold over the past 30 years. The clinical and economical importance of diabetes is determined by the frequent occurrences of such serious complications as neuropathy, retinopathy and nephropathy. Intensive insulin therapy with regular monitoring of blood glucose (up to 4 measurements daily) and adjustment of the insulin dose accordingly may achieve virtually normal levels of blood glucose and thus decrease the risk of these complications. The present cost-effectiveness-study shows that the higher costs of invasive insulin therapy are offset by savings of 8.114 German marks per patient resulting from the reduction in morbidity and mortality. On the basis of an estimated 5% to 10% type 1 diabetes among the total diabetic population (prevalence 4.9%), potential saving of 1.62 to 3.24 billion marks are calculated for Germany.     

Reversed midgut rotation in a neonate: case report with a brief review of the literature

The epidemiological evidence that only a subset of diabetic patients are susceptible to renal damage and the demonstration of clear familiar clustering of diabetic nephropathy are consistent with the possibility that genetic factors may explain the liability to or protection from renal disease of diabetic patients. A predisposition to hypertension and cardiovascular disease may be an important determinant of susceptibility to renal disease and its cardiovascular complications in diabetes since raised blood pressure [1] and an increased frequency of cardiovascular disease [2] are more prevalent in parents of diabetic patients with nephropathy. These results have raised growing interest in the search for intermediate phenotypes significantly associated with diabetic nephropathy, poorly influenced by environment, stable with age, easy to quantify and possibly dependent upon a single major gene effect. Such intermediate phenotypes can be useful for early diagnosis and would help clarify the molecular mechanisms leading to diabetic nephropathy. An elevation of Na+/H+ antiporter activity has consistently been associated with diabetic renal disease both in insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) patients, making this cell membrane exchanger system an ideal intermediate phenotype for the study of diabetic nephropathy.     

What degree of glycemic control can be obtained in diabetics?

In diabetic patients, blood glucose should be controlled to a level which prevents acute metabolic complications, forestalls the development of micro and macroangiopathic complications and remains compatible with good quality of life. Recent interventional trials in both insulin-dependent and non-insulin-dependent patients have helped identify this target glucose level. Maintaining HbA1c between 7 and 7.5% appears to be a realistic objective with minimum risk of severe hypoglycemia. This goal, which may be difficult to reach in certain patients, can only be achieved through the co-ordinated efforts of patients and health care providers. The ideal system includes patient education, renewed training for general practitioners who care for most of the non-insulin-dependent as well as a large number of insulin-dependent diabetic patients in France, close follow-up with regular consultations (calling upon specialists when therapeutic adaptations are required) and an organized system of nursing care by specially trained caregivers. The extra cost of this combined organization is to be balanced against expenditures for complications of diabetes.     

Care of patients with diabetic nephropathy

Diabetic nephropathy is one of the main causes of chronic renal failure in developed countries. The genesis and development of diabetic nephropathy is associated in both types of diabetes with a more rapid progression of other secondary complications and an increased mortality, in particular cardiovascular mortality. The main causes of development of diabetic nephropathy are prolonged hyperglycaemia along with a so far not elucidated inborn disposition. The course of diabetic nephropathy is characterized more clearly in type 1 diabetes. The clinically manifest stage is already irreversible and in the course of years it develops into chronic renal failure. Preventive and curative measures include maintenance of optimal metabolic control, systematic control of blood pressure, in particular by ACE-inhibitors, and a reduction of protein intake. Systematic multidisciplinary collaboration in care for patients with diabetic nephropathy helps to prevent the progression of other secondary complications such as diabetic foot and diabetic retinopathy. At present in the Czech Republic dialysis methods substituting renal function are available to practically all patients with diabetic nephropathy. As regards survival time and quality of life the optimal method of renal function replacement for patients in the terminal stage of diabetic nephropathy is transplantation.     

Does the presence of diabetic nephropathy in parents influence the metabolic response in the offspring?

Non-insulin dependent (Type 2) diabetes mellitus (NIDDM) and long-term complications such as nephropathy have a strong genetic predisposition. Insulin resistance is thought to be a pathogenetic factor, predisposing genetically prone individuals to develop the microvascular complications of diabetes. To test these hypotheses, two groups of young individuals were studied: 28 offspring of parents having NIDDM and diabetic nephropathy (group 1) aged 29.5 +/- 6.1 years, BMI 25.2 +/- 4.7 kg m(-2) and 31 offspring of diabetic parents with no history of nephropathy, aged 31.6 +/- 4.1 years and BMI 26.3 +/- 4.9 kg m(-2) (group 2). All underwent a standard oral glucose tolerance test with measurement of serum insulin levels and serum lipid profile. Urine albumin:creatinine ratio (A/C ratio) and blood pressure were also recorded. Diabetes was detected in 2/28 (7.1%) and 3/31 (9.7%) and IGT was detected in 5/28 (25%) and 8/31 (25%) of groups 1 and 2, respectively. These differences were not statistically significant, but were higher than in a group of non-diabetic controls with healthy parents. Comparison of the normoglycaemic subjects (19 and 20 in group 1 and 2, respectively) showed no significant differences between blood pressure readings, fasting and 2 h plasma glucose, and lipid profiles. Plasma insulin values, fasting and 2 h, and the area under the graph were also similar in both groups, indicating an absence of higher insulin response in group 1 in comparison with group 2. These values were also not different from those in the non-diabetic controls. A delay in insulin response to glucose was noted in many of the offspring as indicated by a low deltaI/deltaG at 30'. We conclude that offspring of diabetic parents with nephropathy do not show higher risk of glucose intolerance or insulin resistance compared to those with diabetic parents without nephropathy. The relatively high plasma glucose values in the presence of normal insulin secretion in both groups of offspring of diabetic parents suggest the presence of insulin resistance.     

Microalbuminuria in non-insulin-dependent diabetes mellitus. Implications for renal survival

Microvascular and macrovascular disease cause considerable mortality and morbidity both among patients with non-insulin-dependent diabetes mellitus and those with insulin-dependent diabetes mellitus. Furthermore, non-insulin-dependent and insulin-dependent diabetes mellitus overlap in their pathogenesis as well as short- and long-term complications. In the diabetic patient, genetic susceptibility as well as other factors, ie, microalbuminuria, hypertension, high protein intake, blood glucose control, etc, ultimately culminate in a diffuse disease process, eg, diabetic vascular and/or renal disease. Early predictors of susceptibility for development of renal disease in diabetic subjects would help focus our treatment strategies. The role of microalbuminuria as a prognostic marker for the major complications of insulin-dependent diabetes mellitus has been previously reviewed. We reviewed the role of microalbuminuria as prognostic marker for progression of diabetic renal disease in subjects with non-insulin-dependent diabetes mellitus. We examined treatment strategies to lower microalbuminuria and its associated impact on disease progression.     

Optimizing antihypertensive therapy in patients with diabetic nephropathy

The number of cases of diabetic nephropathy is increasing, especially among patients with non-insulin-dependent diabetes mellitus (NIDDM). It is difficult to prevent the occurrence or progression of NIDDM, and current levels of treatment are below standard. According to one study, actuarial 5-year survival rates are only about 38% for patients with insulin-dependent diabetes mellitus and 9% for those with NIDDM receiving renal replacement therapy. Because cardiovascular diseases are responsible for more than half of these deaths, hypertension, as a major contributing factor to cardiac death, is a crucial component in the therapy for such patients. It is well established that lowering blood pressure is an important preventive measure to be taken in patients with diabetic nephropathy; blockade of the renin-angiotensin system offers benefits beyond lowering blood pressure in type I diabetic nephropathy. Two major trials are currently underway to determine the effects of angiotensin II receptor antagonists on nephropathy in patients with NIDDM. The Irbesartan Diabetic Nephropathy Trial (IDNT) has already enrolled approximately 85% of the proposed 1650 NIDDM patients to be randomly assigned to placebo, irbesartan or amlodipine. Baseline characteristics of the initial cohort are presented. In light of the well-documented case for blockade of the renin-angiotensin system in diabetes, the potentially superior blockade afforded by angiotensin II receptor antagonists, and the superior tolerability of these agents, trials such as the IDNT take on special importance for the treatment of diabetic patients. From these data may come the justification for the belief that angiotensin II receptor antagonists impart greater benefits in the treatment of diabetes than merely their well-documented role in lowering blood pressure.     

Type II diabetic nephropathy: its clinical course and therapeutic implications

Type II diabetes is responsible for more end-stage renal disease in the United States than any other single condition. Until recently, the majority of research in diabetic nephropathy has focused on patients with type I diabetes despite the fact that type II nephropathy is a more prevalent condition. The notion that there are major differences between the nephropathy of these two types of diabetes is not supported by recent literature. The biggest difference appears to be related to ethnic risk. Histopathologic differences are now being described as well. Clinical interventional trials are few compared to type I diabetes; however, it seems that maneuvers that improve renal prognosis in patients with type I diabetes (blood pressure control, blood glucose control, and the use of angiotensin-converting enzyme inhibitors) apply to the type II population as well. Some of the calcium channel blockers lower proteinuria to a degree that suggests renoprotection and may further improve outcome.     

Diuretics and diabetes mellitus

The term "diuretics" describes a concerning pharmacological action and side effects heterogeneous class of drugs. The special advantage of using diuretics includes reducing edema and expanded plasma volume often associated with hypertension and cardiovascular disease. Diuretics are one of the 5 major classes of antihypertensive agents recommended for the initial drug therapy of hypertension. However, currently treatment of hypertension with diuretics is controversial, because of potentially adverse effects on the cardiovascular risk profile, including deterioration in glucose control especially in patients with impaired glucose tolerance. Additionally there is concern about excess mortality associated with diuretic therapy and diabetes mellitus. The metabolic side effects on glucose metabolism and lipid profile are related to the type of diuretic and its dosage. The adverse effects of thiazides on insulin action, glycemia and lipid profile are dose dependent and can be minimized by using low doses. In contrast, indapamide seems not to alter glucose metabolism and lipid profile. The choice of diuretic depends on concomitant disease. In patients with nephropathy potassium sparing agents should not be used, however furosemid can be used even in high doses. Beside focus on indication of diuretics in patients with diabetes and their metabolic side effects treatment of therapy resistant hypertension in these patients are discussed in this review.     

Target blood pressure with antihypertensive therapy and 24-hour-RR measurement

In younger and middle-aged patients treatment should lower the blood pressure to below 140/90 mmHg and in the elderly aged 65 and more to 160/90 mmHg. Numerous interventional studies have shown that this can appreciably reduce the complications of hypertension. However, account must always be taken of the individual risk, so that in a particular case, it might be desirable to aim for lower values, for example, in diabetic nephropathy or when there is a summation of risks. The question as to whether there is a "point of reversal", that is, a renewed increase in complications associated with too great lowering of the blood pressure is still controversial. What is certain is that a lowering of blood pressure that is too rapid and too great can harm the patient with coronary or cerebral vascular stenoses. Better control of the blood pressure is enabled by the 24-hour blood pressure measurement by recording "office hypertension" or "office normotension", intermittent hypertensive or hypotensive phases and, in particular the nocturnal course of the blood pressure (no physiological dip/too pronounced dip).     

Increased expression of intercellular adhesion molecule-1 (ICAM-1) in diabetic rat glomeruli: glomerular hyperfiltration is a potential mechanism of ICAM-1 upregulation

Mononuclear cells, including monocytes/macrophages and T-cells, are considered to be involved in the progression of diabetic nephropathy, although the mechanism of their recruitment into diabetic glomeruli is unclear. The intercellular adhesion molecule-1 (ICAM-1) promotes the infiltration of leukocytes into atherosclerotic lesions as well as inflammatory tissues. In the present study, we investigated the expression of ICAM-1 in the glomeruli of streptozotocin-induced diabetic rats. The expression of ICAM-1 was increased significantly during the early stage of diabetes. The number of mononuclear cells, primarily monocytes/macrophages and lymphocytes, was significantly increased in diabetic glomeruli. Mononuclear cell infiltration into diabetic glomeruli was prevented by anti-ICAM-1 monoclonal antibody. Insulin treatment decreased ICAM-1 expression and mononuclear cell infiltration. The ICAM-1 expression on cultured human umbilical vein endothelial cells was not induced under high glucose culture conditions. Glomerular hyperfiltration is a characteristic change in the early stage of diabetic nephropathy. Treatment with aldose reductase inhibitor, which prevented glomerular hyperfiltration without changes in blood glucose levels, decreased ICAM-1 expression and mononuclear cell infiltration. Moreover, we examined the ICAM-1 expression in the glomeruli of the 5/6 nephrectomized rat, which is a model for glomerular hyperfiltration without hyperglycemia. The ICAM-1 expression and infiltration of mononuclear cells was significantly increased in the glomeruli of 5/6 nephrectomized rats. We conclude that ICAM-1 is upregulated and promotes the recruitment of mononuclear cells in diabetic glomeruli. Moreover, glomerular hyperfiltration that occurs in the early stage of diabetic glomeruli may be one of the potential mechanisms of ICAM-1 upregulation in diabetic nephropathy.     

Insulin resistance implications for type II diabetes mellitus and coronary heart disease

PURPOSE: To review information on the implications of insulin resistance for type II diabetes mellitus (non-insulin-dependent diabetes mellitus) and coronary heart disease, and to derive guidance from this information for the management of these conditions. DATA SOURCES: A MEDLINE search of English-language articles published between 1985 and July 1996, and review of the bibliographies of articles obtained through the MEDLINE search and textbooks. STUDY SELECTION: Primary research articles, reviews and perspectives on the epidemiology of diabetes and cardiovascular diseases and on intervention outcomes in these diseases. DATA EXTRACTION: Study design and quality were assessed, with particular attention to methods, study population size and other characteristics. Conclusions of review articles and perspectives were analyzed critically. DATA SYNTHESIS: Type II diabetes is associated with a two- to fourfold excess of coronary heart disease, compared to nondiabetic populations. In most studies, glycemia and duration of clinical diabetes were found to be only weak risk factors for coronary heart disease. Conventional coronary heart disease risk factors such as dyslipidemia and hypertension have been associated with coronary heart disease in type II diabetes subjects. Hyperinsulinemia and insulin resistance have been predictive of the development of type II diabetes and, in some studies, of coronary heart disease. CONCLUSION: Strategies to prevent the development of coronary heart disease in diabetic and possibly prediabetic subjects should emphasize a multifactorial approach, including: a) improved glycemic control; b) aggressive treatment of risk factors for coronary heart disease, including insulin resistance; c) primary prevention of NIDDM; and d) use of glucose lowering agents that improve insulin sensitivity and cardiovascular risk factors.     

Diabetes mellitus

The effective management of diabetes in children and teens requires a daily balancing of insulin administration, food intake, and exercise. To optimize outcome and avoid the neuropathic and microcirculatory effects of hyperglycemia, blood glucose levels should be maintained within a targeted range, which can be accomplished with frequent evaluation and adjustment of the overall treatment regimen. This requires meticulous attention to the disease not only by the patient and family, but by school personnel, baby sisters, coaches, and other individuals responsible for the child's welfare. Diabetes must be diagnosed as early as possible once the signs and symptoms of insulin deficiency have developed to avoid DKA and the associated risks of this acute metabolic disturbance. In addition, careful monitoring of patient progress and assurance that osmolality is reduced gradually without a rapid decrease in the serum sodium level may be required to help prevent cerebral edema associated with DKA. Individuals at risk for autoimmune diabetes should be offered the option of diabetes screening, and if appropriate, entered into diabetes prevention trials. With these aggressive measures, it is possible to decrease the acute complications and the long-term morbidity of this chronic disease and the tremendous negative impact that it has on the health-care system.