The elderly type II diabetic: a treatment challenge

Type II or noninsulin dependent diabetes mellitus is the predominant type of diabetes in the elderly. Complexities of diabetes management with elderly patients are discussed, including differences in presenting signs and symptoms of the disease, treatment complications that occur with concomitant illnesses or age-related physiological changes, and drug interactions that can lead to either hypo- or hyperglycemia. The goals of treatment are discussed. Standard therapies, including diet, exercise, and medications, are reviewed with the special considerations of the geriatric patient in mind.     

Premature peripheral vascular disease: clinical profile and abnormal lipid peroxidation

Type 2 diabetes is extremely common and increasing in the United States. The pathophysiology of type 2 diabetes is a combination of increased insulin resistance and inadequate secretion. The main risk factors for diabetes are family history, obesity, sedentary lifestyle, ethnic background, age, and a history of gestational diabetes. Diet and exercise, the cornerstones of diabetes management, will improve insulin sensitivity and indirectly augment insulin secretion. Until recently, the only pharmacological approaches to diabetes were sulfonylureas and insulin, which either augment insulin secretion or replace insulin, thus acting only on the insulin side of the equation. Recently, a series of new drugs have become available that are capable of decreasing hepatic glucose output (metformin), slowing postprandial glucose absorption (acarbose), and improving peripheral insulin sensitivity (troglitazone). With these drugs, either alone or in combination, and behavioral therapies, it is now feasible to achieve good to outstanding glycemic control in most individuals with type 2 diabetes.     

The signals for starvation response are transduced through elevated [Ca2+]i in Dictyostelium cells

Selecting antiretroviral therapies for human immunodeficiency virus type 1-infected persons is complicated by the availability of a vast number of potentially useful drug combinations and by extensive variation among patients in their resistance to various drugs. AIDS clinical trials have used designs in which a handful of drug regimens in a few patient classes can be compared. Here is proposed implementation of innovative designs with factorial structure that permit assessment of many treatment arms and patient classes in a single trial; when and how they can be appropriately used are discussed. These designs are efficient, permit systematic investigation of correlations between genetic mutations and in vivo drug resistance, and provide insight into important drug interactions in people that conventional designs are unable to provide. Through creative application of these designs, identification of superior drug combinations and the science of understanding in vivo joint drug dynamics and genotypic resistance will progress at an optimum pace.     

Type 2 diabetes: patient education and home blood glucose monitoring. 3

Successful treatment of type 2 diabetes requires the interaction of the patient, his or her family, and a variety of healthcare professionals. Education is the most powerful tool doctors have to convince patients, especially those who are asymptomatic, of the serious complications that can result from uncontrolled diabetes. Home blood glucose monitoring is a key to the doctor-patient partnership. Physicians may have to consider a patient's cultural and dietary customs in developing a manageable program of weight loss, diet, and physical activity, the most effective forms of treatment. Referrals should be made to local diabetes organizations with patient support programs, when available. Patient empowerment and education are key to effective management.     

Chronic autoimmunity of type I diabetes

A considerable body of data supports the hypothesis that type I diabetes is a chronic progressive autoimmune disorder. Individuals with very high probability of progressing to diabetes can now be readily identified. Assays for autoantibodies reacting with insulin (IAA), glutamic acid decarboxylase (GAD65AA), and the neuroendocrine tyrosine phosphatase ICA512/IA-2 (ICA512AA) allow for the identification of more than 95% of individuals developing type I diabetes. The expression of a single autoantibody does not indicate high risk for diabetes and in general, prediabetic individuals express a series of biochemically defined autoantibodies. Levels of such autoantibodies are usually stable over years of follow-up. Unusual variants of autoantibody expression (e.g. GAD-ICA with high titers of GAD65 autoantibodies as the sole autoantibody) have low prognostic significance. Given the presence of multiple autoantibodies, low first phase insulin secretion (following intravenous glucose) is the best predictor of time to diabetes onset. Measurement of autoantibodies can now be automated and applied to large populations such that screening and prediction in the general population is now feasible. We favor the hypothesis that insulin may be the primary autoantigen for type I diabetes, and therapies which after the immune response to insulin may lead to safe and effective preventive modalities.     

Therapy for type 2 diabetes mellitus

Type 2 diabetes mellitus is a common, chronic disease affecting nearly 6% of the adult US population. It remains a leading cause of morbidity and mortality in Wisconsin as well as the country. Multiple lines of evidence show that controlling blood glucose in patients with type 2 diabetes can significantly decrease the development of and/or progression of microvascular complications as well as the macrovascular complications of diabetes. There are now four different classes of oral medications which are available to treat diabetes-sulfonylureas, biguanides, thiazolidinediones, and alpha-glucosidase inhibitors. Each class works differently to treat the underlying defects of diabetes which include impaired insulin secretion, insulin resistance and exaggerated postprandial hyperglycemia. This article will compare and contrast the different agents available, including appropriate use of each agent as monotherapy and in combination therapy. It will also discuss use of insulin in the patient who has failed oral therapy. Rational use of these tools, tailored for the individuals metabolic abnormalities, should allow for good glycemic control in the majority of patients with type 2 diabetes mellitus. Relaxation, massage, opium, and moderate exercise were among the recommended options for treatment of diabetes mellitus nearly 100 years ago. In the late nineteenth century, diabetes was a poorly characterized disorder, which was increasing in prevalence even at that time. Today, the underlying defects contributing to the development of type 2 diabetes are better understood, and include peripheral insulin resistance, relative pancreatic beta-cell insufficiency, increased hepatic glucose output, and an exaggerated postprandial glucose excursion. However, despite our better understanding of the disease, the prevalence of type 2 diabetes continues to increase in the US, now afflicting over 6% of the population. As our population ages and the proportion of obese people increases, we can expect to see a marked increase in the prevalence of diabetes in the future. Fortunately, our treatment options for type 2 diabetes have expanded remarkably within the last few years. Along with these new treatment options comes the exciting, although likely expensive, possibility of prevention of type 2 diabetes in at risk individuals.     

Insulin dependent (type 1) diabetes mellitus in advanced age

In everyday praxis diabetes mellitus diagnosed over the age of fifty years, means generally type 2 diabetes. Authors present cases where diabetes, beginning in advanced age, showed typical classical diabetic symptoms, like polyuria, polydipsia, loss of bodyweight. Apart from these signs a rapid decompensation of carbohydrate metabolism characterises this diabetes form. The most significant features are the rapid decrease of serum immunoreactive insulin and C-peptide levels, what is characteristic for the diminishing insulin secretory capacity. The patients had to be switched to insulin therapy within maximum 6 weeks. These patients can be easily differentiated both from type 2 and from the slowly progressing type 1 subtype. We suppose that the pathomechanism of this type of diabetes differs from the classical insulin-dependent form, beginning in young age.     

Estimated benefits of glycemic control in microvascular complications in type 2 diabetes

BACKGROUND: The benefits of intensive glycemic control in patients with type 2 diabetes are not well quantified. It is therefore not clear which patients will benefit most from aggressive glycemic control. OBJECTIVE: To evaluate the efficacy of glycemic control in type 2 diabetes. DESIGN: Markov decision model. PATIENTS: Diabetic patients at a health maintenance organization. MAIN OUTCOME MEASURES: Risks for developing blindness and end-stage renal disease; number of patients and patient-years needed to treat to prevent complications. RESULTS: For a patient in whom diabetes developed before 50 years of age, reducing hemoglobin A1c levels from 9% to 7% results in an estimated 2.3-percentage point decrease (from 2.6% to 0.3%) in lifetime risk for blindness due to retinopathy. The same change in a patient with diabetes onset at 65 years of age would be expected to decrease the risk for blindness by 0.5 percentage points (from 0.5% to < 0.1%). However, the Markov model predicts substantially greater benefit when moving from poor to moderate glycemic control than when moving from moderate to almost-normal glycemic control. Targeting less than 20% of the patients at one health maintenance organization for intensified therapy may prevent more than 80% of the preventable patient-time spent blind. The risks for end-stage renal disease and the risk reduction provided by improved glycemic control are lower than those for blindness. CONCLUSIONS: This probability model, based on extrapolation from the experience with type 1 diabetes, suggests that patients with early onset of type 2 diabetes will accrue substantial benefit from almost-normal glycemic control. In patients with later onset, moderate glycemic control prevents most end-stage complications caused by microvascular disease. These results have important implications for informing patients and allocating health care resources.     

Antecedents of dental anxiety: learned responses versus personality traits

Patients recovering from alcohol and other drug addiction have unique medical and pharmacological needs. Careful selection of medications call decrease the risk of relapse. Angiotensin-converting enzyme inhibitors and calcium channel-blocking medications are excellent choices to treat hypertension. Most gastrointestinal problems resolve with abstinence and can be treated nonpharmacologically. In managing pain, physicians should avoid narcotics and use nonpharmacological treatment whenever possible. Treating recovering patients with HIV can be challenging because of the side effects of many of the antiviral medications. The newer antiviral agents have fewer side effects and contraindications. Commonly used remedies for colds and cough can cause a relapse to drug use. Patients with diabetes mellitus need to be monitored very closely in early recovery to prevent hypoglycemia. Frequently a team approach is helpful in managing the medication needs of patients in recovery.     

A review of the incorporation of complementary and alternative medicine by mainstream physicians

BACKGROUND: Studies suggest that between 30% and 50% of the adult population in industrialized nations use some form of complementary and/or alternative medicine (CAM) to prevent or treat a variety of health-related problems. METHOD: A comprehensive literature search identified 25 surveys conducted between 1982 and 1995 that examined the practices and beliefs of conventional physicians with regard to 5 of the more prominent CAM therapies: acupuncture, chiropractic, homeopathy, herbal medicine, and massage. Six studies were excluded owing to their methodological limitations. RESULTS: Across surveys, acupuncture had the highest rate of physician referral (43%) among the 5 CAM therapies, followed by chiropractic (40%) and massage (21%). Rates of CAM practice by conventional physicians varied from a low of 9% for homeopathy to a high of 19% for chiropractic and massage therapy. Approximately half of the surveyed physicians believed in the efficacy of acupuncture (51%), chiropractic (53%), and massage (48%), while fewer believed in the value of homeopathy (26%) and herbal approaches (13%). CONCLUSIONS: This review suggests that large numbers of physicians are either referring to or practicing some of the more prominent and well-known forms of CAM and that many physicians believe that these therapies are useful or efficacious. These data vary considerably across surveys, most likely because of regional differences and sampling methods, suggesting the need for more rigorous surveys using national, representative samples. Finally, outcomes studies are needed so that physicians can make decisions about the use of CAM based on scientific evidence of efficacy rather than on regional economics and cultural norms.     

Non-diuretic-based antihypertensive therapy and potassium homeostasis in elderly patients

Aging and hypertension are associated with a progressive decline in renal blood flow and renal function. As a result, physicians planning therapeutic strategies to control blood pressure need to consider these changes and how they relate to potassium homeostasis, particularly in elderly patients. Commonly used antihypertensive drugs such as beta-blockers, angiotensin converting enzyme inhibitors and potassium-sparing diuretics need to be used with increasing caution in patients with declining renal function. This is especially important in patients with diabetes who may also have type IV renal tubular acidosis, and in patients given concomitant therapy with non-steroidal anti-inflammatory drugs. Other therapies such as calcium channel blockers, particularly those that gate atrioventricular nodal conduction, also need to be used with care in people with significant renal insufficiency and hyperkalemia, as this clinical scenario may result in a greater risk of complete heart block.     

Physician perspectives on unconventional cancer therapies

The popularity of unconventional therapies has grown dramatically in recent years. This paper reports on the results of a pilot study investigating the perspectives of physicians involved with cancer care regarding their reactions to this trend and their ways of trying to meet associated challenges. Nine oncologists, nine general practitioners, and one surgeon were interviewed over the telephone, employing open-ended questions. The physicians were unanimously interested in having information available about unconventional therapies. They also expressed a desire to be supportive of patient choices in this area, provided conventional therapy was not compromised. However, there was little interest in initiating communication about unconventional therapies, with most seeing such discussions as a poor use of their time. Suggestions for future research, as well as educational and policy strategies, are addressed.     

Repaglinide, a novel, short-acting hypoglycemic agent for type 2 diabetes mellitus

Repaglinide is a new, short-acting, insulin-releasing agent recently approved for the monotherapy of type 2 diabetes mellitus, and in combination with metformin in patients failing repaglinide or metformin monotherapy. Repaglinide appears to trigger insulin release by regulating adenosine triphosphate-sensitive potassium channels on the surface of pancreatic beta cells, which in turn affect calcium influx, the principal mediator of insulin release. Repaglinide mainly affects postprandial plasma glucose concentrations. It reduces glycosylated hemoglobin concentrations by 1-2% U. The agent's short duration of action may lessen the risk of long-lasting hypoglycemia and of down-regulation of beta cell sensitivity (the latter promoting secondary drug failure), although data are sparse in this regard. Its major adverse effect is hypoglycemia. Its role in the therapy of type 2 diabetes is unclear at present, vis-à-vis its use instead of or in combination with other antidiabetic agents other than metformin. The need for multiple daily doses, based on its brief duration of action, may be a barrier to compliance.     

Type 2 diabetes: causes, complications, and new screening recommendations. I

Type 2 diabetes mellitus, one of the most prevalent and disruptive diseases in our older population, occurs in approximately 10% of persons over age 65. Its cause is usually a combination of deficient insulin production and resistance to insulin. In approximately one-half of those with diabetes, symptoms occur slowly over time and escape diagnosis. Complications include cardiovascular disease with myocardial infarction and stroke, nephropathy, retinopathy, peripheral neuropathy, and sexual dysfunction. Risk factors include age, family history, obesity, and sedentary lifestyle. Screening and early diagnosis are important secondary means of prevention, but physicians should also think about primary prevention based on family history, diet, and physical activity.     

Disruption of IRS-2 causes type 2 diabetes in mice

Human type 2 diabetes is characterized by defects in both insulin action and insulin secretion. It has been difficult to identify a single molecular abnormality underlying these features. Insulin-receptor substrates (IRS proteins) may be involved in type 2 diabetes: they mediate pleiotropic signals initiated by receptors for insulin and other cytokines. Disruption of IRS-1 in mice retards growth, but diabetes does not develop because insulin secretion increases to compensate for the mild resistance to insulin. Here we show that disruption of IRS-2 impairs both peripheral insulin signalling and pancreatic beta-cell function. IRS-2-deficient mice show progressive deterioration of glucose homeostasis because of insulin resistance in the liver and skeletal muscle and a lack of beta-cell compensation for this insulin resistance. Our results indicate that dysfunction of IRS-2 may contribute to the pathophysiology of human type 2 diabetes.     

Intensive treatment of type 1 diabetes

There have been amazing advances for the treatment of type 1 diabetes. As clinicians proceed into the twenty-first century, it is appropriate to reflect both about accomplishments and about the prospects of improved therapeutic options. Regarding the former, perhaps no advance can be compared to the discovery of insulin. Since then, the improvements in therapy have appeared to be too slow for physicians, patients, and their families. In actuality, over the past 20 years, the pace for the development of new tools for the treatment of this once fatal disease has been remarkable. The treatment of type 1 diabetes has evolved with advances in the treatment of microvascular, neuropathic, and macrovascular complications. The future is even more promising, with the possibility of even preventing the disease before the development of hyperglycemia. The challenge for the present is teaching all individuals involved with the management of patients with type 1 diabetes to manage the condition as effectively as possible.     

Issues surrounding tight glycemic control in people with type 2 diabetes mellitus

OBJECTIVE: To review the prospective evidence surrounding the issue of tight glycemic control in people with type 2 diabetes mellitus and resultant long-term complications. DATA SOURCE: Conference proceedings and a MEDLINE search (1966-February 1998) identified pertinent English-language publications on type 2 diabetes in humans. Key search terms included insulin resistance, diabetes mellitus, non-insulin-dependent, macrovascular complications, microvascular complications, and intensive glycemic control. STUDY SELECTION: Selection of prospective epidemiologic and clinical studies were limited to those focusing on the management of type 2 diabetes. All articles with pertinent information relevant to the scope of this article were reviewed. DATA SYNTHESIS: The pathophysiology of type 1 and type 2 diabetes differ; however, both share chronic complications that significantly affect morbidity and mortality. People with type 1 diabetes have an absolute deficiency of insulin, whereas people with type 2 diabetes have varying degrees of insulin resistance and an inadequate compensatory insulin secretory response. The Diabetes Control and Complications Trial (DCCT) has clearly indicated that intense control of blood glucose in type 1 diabetes prevents and slows the progression of microvascular (i.e., retinopathy, nephropathy) and neuropathic complications. The Kumamoto study showed similar results in nonobese patients with type 2 diabetes. Intense insulin therapy in both populations has proven advantageous, thus supporting a common pathophysiologic process for the microvascular and neuropathic complications. Trends were seen toward fewer macrovascular (atherosclerotic disease) complications in the intensive insulin arm of the DCCT. Conversely, trends were seen toward an increase in macrovascular complications in the VA Cooperative study in people with type 2 diabetes using intensive insulin therapy. This may suggest a discordance in the pathophysiology of macrovascular disease between type 1 and type 2 diabetes. Additionally, it remains uncertain whether tight glycemic control prevents the onset or slows the progression of macrovascular disease. Two studies (the University Group Diabetes Program and the Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type 2 Diabetes) to date have examined pharmacotherapy options for patients with type 2 diabetes and resultant macrovascular complications. It has yet to be determined whether any therapeutic intervention will decrease the morbidity and mortality of macrovascular disease in this population. CONCLUSIONS: In type 2 diabetes, limited prospective evidence does support tight glycemic control to help prevent or slow the progression of microvascular and neuropathic complications. It is uncertain whether tight glycemic control decreases macrovascular complications and which pharmacotherapeutic agent(s) is/are the best options. However, therapy that improves glucose control in combination with aggressive risk factor management should be initiated and enforced in patients with type 2 diabetes in an effort to reduce long-term complications.     

The genetic basis of type 2 diabetes mellitus: impaired insulin secretion versus impaired insulin sensitivity

Despite the fact that it is the prevalent view that insulin resistance is the main genetic factor predisposing to development of type 2 diabetes, review of several lines of evidence in the literature indicates a lack of overwhelming support for this concept. In fact, the literature better supports the case of impaired insulin secretion being the initial and main genetic factor predisposing to type 2 diabetes, especially 1) the studies in people at high risk to subsequently develop type 2 diabetes (discordant monozygotic twins and women with previous gestational diabetes), 2) the studies demonstrating compete alleviation of insulin resistance with weight loss, and 3) the studies finding that people with type 2 diabetes or IGT can have impaired insulin secretion and no insulin resistance compared with well matched NGT subjects. The fact that insulin resistance may be largely an acquired problem in no way lessens its importance in the pathogenesis of type 2 diabetes. Life style changes (exercise, weight reduction) and pharmacological agents (e.g., biguanides and thiazolidendiones) that reduce insulin resistance or increase insulin sensitivity clearly have major beneficial effects (122, 144-146, 153-155).     

The third version of the Diabetes Attitude Scale

OBJECTIVE: The objective of this study was to develop a third version of the Diabetes Attitude Scale (DAS-3) that is congruent with current scientific knowledge about diabetes, has improved subscale internal reliability scores, and is shorter than the earlier versions of this instrument. RESEARCH DESIGN AND METHODS: The second DAS was revised and rewritten by a panel of diabetes experts, including patients, associated with the University of Michigan Diabetes Research and Training Center. The revised version of the instrument was sent to physicians, nurses, dietitians, and patients with diabetes. Completed and usable questionnaires were obtained from 384 patients with diabetes, 321 physicians, 540 nurses, and 569 dietitians. The total number of surveys used for these analyses was 1,814. RESULTS: The study resulted in a revised DAS with 33 items and five discrete subscales. The subscales were attitudes toward the following: 1) need for special training to provide diabetes care, 2) seriousness of type 2 diabetes, 3) value of tight glucose control, 4) pyschosocial impact of diabetes, and 5) attitude toward patient autonomy. Overall, the subscale reliabilities of the DAS-3 were superior to the earlier versions of the scale. CONCLUSIONS: The DAS-3 is a valid and reliable general measure of diabetes-related attitudes and is most suitable for comparisons across different groups of health care professionals and/or patients. The DAS-3 is also suitable for the evaluation of patient and/or professional education programs if those programs focus on the specific topic areas measured by the five DAS-3 subscales.     

Diabetic foot ulcers: prevention, diagnosis and classification

Diabetic ulcers are the most common foot injuries leading to lower extremity amputation. Family physicians have a pivotal role in the prevention or early diagnosis of diabetic foot complications. Management of the diabetic foot requires a thorough knowledge of the major risk factors for amputation, frequent routine evaluation and meticulous preventive maintenance. The most common risk factors for ulcer formation include diabetic neuropathy, structural foot deformity and peripheral arterial occlusive disease. A careful physical examination, buttressed by monofilament testing for neuropathy and noninvasive testing for arterial insufficiency, can identify patients at risk for foot ulcers and appropriately classify patients who already have ulcers or other diabetic foot complications. Patient education regarding foot hygiene, nail care and proper footwear is crucial to reducing the risk of an injury that can lead to ulcer formation. Adherence to a systematic regimen of diagnosis and classification can improve communication between family physicians and diabetes subspecialists and facilitate appropriate treatment of complications. This team approach may ultimately lead to a reduction in lower extremity amputations related to diabetes.