Syndrome X: medical nutrition therapy.

A significant number of Americans are at risk for developing a condition of insulin resistance termed Syndrome X. Dyslipidemia, resistance to insulin, obesity, and blood pressure elevation--the deadly quartet--describe Syndrome X, which increases atherogenic risk and contributes to coronary artery disease. Lifestyle factors such as overeating and physical inactivity play a pivotal role in Syndrome X. This deadly duet has been aptly coined "hyperactive fork" and "hypoactive foot," respectively. In addition, emerging evidence suggests that certain nutrients may help protect against Syndrome X. This review provides a brief discussion of diet and lifestyle factors related to Syndrome X.

Pioglitazone attenuates basal and postprandial insulin concentrations and blood pressure in the spontaneously hypertensive rat.

Subjects with hypertension are hyperinsulinemic and resistant to insulin-stimulated glucose uptake. A similar paradigm is found in the spontaneously hypertensive rat (SHR). These findings suggest the possibility that insulin resistance and hyperinsulinemia may play an important role in blood pressure regulation. Pioglitazone, a thiazolidinedione derivative, sensitizes target tissues to insulin and decreases hyperglycemia and hyperinsulinemia in various insulin-resistant animals. The purpose of this study was to assess the influence of pioglitazone administration on pre- and postprandial glucose and insulin concentrations and determine whether changes in beta-cell secretion resulted in any change in blood pressure measurements. Twelve SHR were fed custom diets ad libitum, six with and six without pioglitazone (20 mg/kg chow). Fasting and postprandial glucose levels were unaltered by pioglitazone treatment. Fasting insulin concentrations were similar at week 1, but were significantly lower (P < .01) in the pioglitazone group at weeks 3 (1.89 +/- 0.3 v7.94 +/- 1.5 ng/mL) and 4 (4.5 +/- 1.4 v9.1 +/- 0.7 ng/mL), compared with the control group. Pioglitazone also significantly (P < .01) lowered postprandial insulin concentrations after an oral glucose challenge. Systolic, mean, and diastolic blood pressures were significantly lower (P < .01), 177 +/- 3 v190 +/- 4.7 mm Hg, 162 +/- 2.1 v175 +/- 5.9 mm Hg, and 156 +/-2.1 v168 +/- 6.2 mm Hg, respectively, in the animals receiving pioglitazone versus the control group. Heart rate, body weight, serum cholesterol, and triglyceride levels were comparable between the two groups. In conclusion, pioglitazone significantly decreased fasting and postprandial insulin concentrations and effectively lowered blood pressure in the SHR.

Type 2 diabetes: glycemic targets and oral therapies for older patients.

In older patients with type 2 diabetes, life expectancy and the presence of microvascular complications determine the appropriate intensity of glucose control. The available antidiabetic agents offer many options for achieving glycemic targets, based on the needs of the individual patient. New stimulators of insulin secretion include glimepiride (a sulfonylurea) and repaglinide (a meglitinide). The biguanide metformin is especially useful in obese, insulin-resistant patients. Alpha-glucosidase inhibitors such as acarbose and miglitol act locally in the GI tract to reduce postprandial excursion in glucose levels. The insulin-sensitizing drug troglitazone enhances insulin-mediated glucose disposal. When troglitazone is used, careful monitoring of patients' liver function is required.

Alcohol-associated diabetes mellitus. A review of the impact of alcohol consumption on carbohydrate metabolism.

Most cases of diabetes mellitus result from decreased insulin secretion (type I, insulin-dependent) or altered insulin action (type II, insulin-independent). Another category, namely, "other" diabetes mellitus-associated conditions, is usually mentioned to distinguish this type of diabetes from the other two categories; this category includes drugs, genetic and endocrine syndromes, and pancreatic disorders. The most common pancreatic disease that causes diabetes mellitus is chronic pancreatitis that results from alcohol abuse. The clinical observation of patients at our institution with long histories of heavy alcohol intake and diabetes mellitus prompted us to review the impact of alcohol on carbohydrate metabolism. In many of these patients, it was notable that they were not obese and they had no immediate family members with diabetes mellitus, raising the possibility that alcohol-associated diabetes mellitus may be a distinct subset of non-insulin-dependent diabetes mellitus that is distinct from type II diabetes mellitus.

Nutritional factors and hypertension.

Hypertension is a major risk factor for coronary artery disease, stroke, renal failure, and peripheral vascular disease. The importance of preventing hypertension and controlling blood pressure in patients with hypertension is well established and is associated with reduced cardiovascular morbidity and mortality rates. Treatment guidelines should consider the merits of dietary changes in addition to pharmacologic therapy in the control of mild hypertension.

'White coat' hyperglycemia.

A visit to a physician's office may provoke an increase in blood pressure. Stress is also a well-known glycemic aggravation, and managing diabetes with ongoing stress is often difficult. Two patients with diabetes mellitus in whom anxiety and stress contributed to transient hyperglycemia that impacted adversely on their diabetes management are presented. "White coat" hyperglycemia should be suspected when the clinical glucose levels are higher than the glucose levels measured by the patient at home and the clinical glycohemoglobin levels. The recognition of white coat hyperglycemia is especially important with the recent findings that intensive therapy effectively delays the onset and slows the progression of diabetic complications in patients with insulin-dependent diabetes mellitus. Failure to appreciate white coat hyperglycemia will increase the risk of hypoglycemic episodes, some of which may be severe and life threatening.

Acute adrenal insufficiency in association with pancreatic carcinoma.

Addison's disease secondary to metastatic cancer to the adrenal gland is underdiagnosed. Prompt diagnosis and treatment is essential and could enhance the quality of life. Cases of adrenal insufficiency produced by metastatic carcinoma are unusual, despite the frequency of carcinomatous metastases to the adrenal glands. The clinical features of adrenal insufficiency are relatively nonspecific and can be easily overlooked in a patient with a malignant neoplasm. We report herein the case of a middle-aged man who presented with adrenal insufficiency in association with pancreatic carcinoma. To our knowledge, this is the first reported case of adrenal insufficiency occurring with adenocarcinoma of the pancreas.

Treatment of mild hypertension. Decision before drugs.

The treatment of mild hypertension by the primary-care physician requires an understanding of its natural history and reflects a balance between patient observation and institution of drug therapy. The diagnosis of mild hypertension in the office is subject to pitfalls such as "white-coat" hypertension and pseudohypertension. For patients presenting with a diastolic blood pressure inconsistent with the presence of end-organ damage, ambulatory blood pressure monitoring may be of value. After a diagnosis of mild hypertension is established, institution of drug therapy is not an immediate issue in low-risk patients lacking end-organ damage. Mild hypertension tends to regress over time; therefore, nonpharmacologic measures of blood pressure reduction should be used first. Echocardiographic assessment of left ventricular mass is a noninvasive method to assess the severity of established cases and can guide decisions regarding aggressiveness of drug therapy. Because patients with mild hypertension make up a heterogeneous population, treatment goals need to be individualized. For patients with ischemic heart disease, reductions in the diastolic blood pressure below 85 mm Hg may produce adverse consequences. In persons suffering from diabetes, congestive heart failure, renal insufficiency, or showing increased left ventricular mass, the absolute reduction in blood pressure is guided by the clinical response of the coexisting disease. Finally, in patients with prior cerebrovascular disease, blood pressure should be lowered to the lowest tolerable level to achieve the maximum improvement in stroke reduction.

Polyunsaturated fats enhance peripheral glucose utilization in rats.

Carbohydrate intolerance is positively correlated with saturated fat consumption. In contrast, individuals consuming diets comprised of polyunsaturated fatty acids (PUFA) have a lower incidence of diabetes mellitus (DM). To test the hypothesis that dietary fats may influence insulin sensitivity, insulin-stimulated glucose utilization was estimated in vivo in rats consuming diets enriched with saturated fatty acids (SFA) (cocoa butter), monounsaturated fatty acid (MUFA) (olive oil), or PUFA derived from corn or fish sources. Each test meal provided (as percentage of calories) 45% carbohydrate, 39% fat, and 16% protein. The meals were consumed over an 8-week period. Metabolic clearance rate (MCR) for glucose was significantly higher (p less than 0.01; 5.69 +/- 0.46 and 5.18 +/- 0.29 ml/kg/min) for diets containing fish and corn oil sources, respectively, when compared to olive oil (4.34 +/- 0.32 ml/kg/min) and cocoa butter (4.61 +/- 0.11 ml/kg/min). Although the MCR between the fish and corn oil diets were not significantly different, the steady state plasma insulin concentration was lower during the fish oil meal (75 +/- 20 microU/ml) when compared to the corn meal (112 +/- 13 microU/ml). Fasting plasma insulin concentrations were significantly lower (p less than 0.01) following the PUFA diets compared to the other two diets. Fasting plasma glucose levels, despite being lower in the fish meal, were insignificantly different among the four test meals. Lastly, body weights were comparable among the four groups tested. These results suggest that diets enriched with PUFA enhance peripheral glucose utilization significantly more than diets comprised of MUFA or SFA sources.(ABSTRACT TRUNCATED AT 250 WORDS)

A morphological and immunohistochemical investigation of endocrine pancreata from obese ob+/ob+ mice.

There is a marked difference in insulin secretion between the ob+/ob+ obese mouse and its non-obese littermate. Numerous peptides have been implicated in the modification of postprandial insulin secretion. In this study, the morphological and immunohistochemical studies of the genetically obese mouse (ob+/ob+) pancreata were compared with control littermates. Additionally, the distribution of gastric inhibitory polypeptide, somatostatin, glucagon, and insulin immunoreactive cells was also quantitated. Hyperglycemia and hyperinsulinemia were verified in the obese mice. The control animals had some islets and ductules with mononuclear infiltrations of a possible immune character. The obese individuals had a marked increase in both number and size of the islets of Langerhans compared with lean controls. The insulin immunocytochemical reaction in the obese pancreatic beta-cells was weaker than that of controls, as was the aldehyde-fuchsin reaction. The glucagon, gastric inhibitory polypeptide, and somatostatin containing cells were intermingled with the beta-cells. In contrast, the control animals showed a peripheral localization of these cell types. The morphometric analysis of the obese pancreas showed a decreased proportion of non-beta cells within the islets but not in total pancreatic volume in comparison with controls. The obese mouse also had cavities filled with eosin-stained material among numerous beta-cells. No complete epithelial lining distinguished these formations from the surrounding islet cells. The content of the cavities was not stained by any of the immunocytochemical reactions applied. In conclusion, the pancreatic islets of the ob+/ob+ mouse show marked differences in both morphological and immunocytochemical characteristics if compared with control littermates. These differences in architecture may be related to the eventual development of diabetes mellitus in the ob+/ob+ mouse.

Effect of acarbose on carbohydrate and lipid metabolism in NIDDM patients poorly controlled by sulfonylureas.

The ability of acarbose to lower plasma glucose concentration was studied in 12 patients with non-insulin-dependent diabetes mellitus (NIDDM) who were poorly controlled by diet plus sulfonylurea drugs. Patients were studied before and 3 mo after the addition of acarbose to their treatment program, and a significant improvement in glycemic control was noted. Although the decrease in fasting plasma glucose concentration was modest (12.0 +/- 0.8 to 10.8 +/- 0.3 mM), average postprandial plasma glucose concentration decreased by 3.4 mM. When acarbose therapy was discontinued in 5 patients, plasma glucose levels rapidly returned toward pretreatment levels. In addition to the improvement in glycemia, acarbose treatment also led to a significant reduction in HbA1c (7.4 +/- 0.2 to 6.4 +/- 0.2%, P less than 0.01) and triglyceride (2.4 +/- 0.1 to 2.1 +/- 0.1 mM, P less than 0.01) concentrations. Neither the plasma insulin response to meals nor insulin-stimulated glucose uptake improved with acarbose therapy, consistent with the view that acarbose improves glycemic control by delaying glucose absorption. Considerable individual variation was noted in the response to acarbose, and the results in 4 patients were dramatic, with striking reductions in both fasting and postprandial glucose concentrations. The addition of acarbose to patients with NIDDM not well controlled by sulfonylureas appears to have significant clinical benefit.

Gastric inhibitory polypeptide mechanisms of augmenting insulin secretion.

The cellular mechanisms whereby gastric inhibitory polypeptide (GIP) augments glucose-dependent insulin secretion remains poorly defined. Since glucose-dependent insulin secretion is modulated by membrane associated phospholipase A2 (PLA2) and intracellular lipoxygenase (LPX) and cyclooxygenase (CO) we hypothesize that GIP's augmentation of insulin secretion involves these enzyme systems. Neonatal rat pancreatic islet cell cultures were preincubated with 5.6mM glucose for 60 minutes. The cultures were then stimulated for 60 minutes with 16mM glucose alone or with GIP with or without the addition of PLA2, LPX, and CO inhibitors. Insulin secretion significantly increased (P less than 0.05) when the glucose concentration was raised from 5.6 to 16mM glucose and this was further augmented by the addition of GIP (P less than 0.05). PLA2 inhibitors significantly (P less than 0.025) decreased 16mM glucose insulin secretion but this was restored by the simultaneous addition of GIP. LPX inhibitors significantly (P less than 0.01) decreased glucose-dependent insulin secretion and this decrease persisted despite the addition of GIP. Simultaneous treatment of islet cell cultures with GIP and CO inhibitors yielded insulin responses that were indistinguishable from CO inhibition alone. These studies suggest that GIP exerts its influence in part by modulating membrane associated PLA2 activity. Furthermore, the formation of intracellular LPX products appears to be a pivotal step in the insulinotrophic action of GIP.

Dissimilar fatty acid composition of standard rat chow.

The lower incidence of coronary heart disease in populations consuming polyunsaturated fatty acids has spurred interest in the possible cardioprotective nature of these fatty acids. Furthermore, the source of dietary fats may modify the natural history of some chronic inflammatory disorders such as rheumatoid arthritis and systemic lupus erythematosus. Some studies examining these issues have involved animals fed a standard chow diet to which the desired fatty acids were added. Our observation that two lots of standard rat chow varied considerably in fatty acid composition, prompted us to analyze two additional standard rat chow lots for fatty acid composition. Each lot was extracted and fatty acid chain length determined by gas chromatography with the percentage of total fatty acids determined by integration. A wide variation in the total saturated (27.4-42.1%), monounsaturated (8.3-30.9%), omega 6 (17.2-44.2%), and omega 3 (3.8-11.2%) fatty acids was observed. By one-way analysis of variance, significant differences (p less than 0.025) between the various lots were observed for total saturated, monounsaturated, and omega 6 fatty acid groups. These findings suggest that fatty acid composition of standard rat chow is not similar. If the baseline fatty acid composition is critical to the experimental design, custom chow diets should be used.

The postprandial response of gastric inhibitory polypeptide to various dietary fats in man.

Gastric Inhibitory Polypeptide (GIP) is secreted in response to oral glucose, amino acid, and fats. In the presence of hyperglycemia, GIP augments nutrient stimulated insulin secretion. Studies looking at the effect of fat on GIP release, however, have focused primarily on corn oil, a polyunsaturated fat. To determine if other fats give similar GIP results to those with corn oil, nine normal subjects underwent four tolerance tests with fats derived from saturated (cocoa butter), monounsaturated (olive oil), or polyunsaturated (corn oil and fish oil) sources. Fifty grams of each triglyceride rich fat were ingested and serum cholesterol, triglyceride, glucose, insulin, and GIP levels were determined over a 180-minute period. Serum cholesterol, triglyceride, glucose, and insulin levels were similar following each fat tolerance test. GIP concentrations, however, were significantly lower (P less than 0.01) with the fish oil, when compared to the other fats studied. Similar GIP responses were observed with olive oil and corn oil, but both were higher than with the cocoa butter. These findings suggest that the source of fatty acids affect GIP secretion. The reason for these differences in serum GIP responses is uncertain, but is not readily explained by changes in serum glucose, insulin, or triglyceride concentrations. Since GIP augments nutrient stimulated insulin release 1-3 hours postprandially, the source of dietary fat consumed as part of a mixed meal could ultimately influence pancreatic beta cell insulin secretion.

The effects of antihypertensive agents on serum lipids and lipoproteins.

Hypertension is a major risk factor for arteriosclerotic vascular disease. Despite intensive antihypertensive intervention, the risk of cardiovascular disease has not declined appreciably. Many of the antihypertensive agents have been shown to elevate total serum cholesterol and triglyceride levels or lower the high-density lipoprotein-cholesterol level. Thus, the antihypertensive agents chosen may negate the beneficial effects of a lower blood pressure. Our purpose is to review all available antihypertensive medications and their influence on lipoprotein metabolism. Choosing the antihypertensive therapy least likely to worsen or precipitate other known cardiovascular risk factors is important. Cost and side effect profiles must also be considered in choosing the best antihypertensive regimen for your patients.

Effect of source of dietary fats on serum glucose, insulin, and gastric inhibitory polypeptide responses to mixed test meals in subjects with non-insulin dependent diabetes mellitus.

We recently demonstrated that normal subjects given mixed test meals of varying fatty acid composition showed significantly greater serum insulin responses to meals enriched with polyunsaturated fat as compared to those in which the fat content was derived from saturated fatty acids. To determine if a similar phenomenon occurs in subjects with non-insulin dependent diabetes mellitus (NIDDM), serum glucose, insulin, C-peptide, and gastric inhibitory polypeptide (GIP) responses to three mixed test meals of varying fatty acid composition were assessed in twelve subjects with NIDDM. Baseline means (+/- SEM) fasting serum glucose concentration was 205 +/- 15 mg/dl and mean glycosylated hemoglobin was 8.5 +/- 0.5%. Fatty acids in the test meals were either saturated fats, or polyunsaturated fats derived from vegetables or fish. Each test meal provided 40% of the subjects' calculated daily caloric requirement and contained approximately 45% carbohydrate, 40% fat, and 15% protein. No appreciable differences in serum glucose, insulin, and C-peptide responses occurred during the three mixed test meals. Although GIP values were higher in the saturated fat and the vegetable meals when compared to the fish meal, the differences did not reach statistical significance. The inability of NIDDM subjects to evoke a greater insulin response to polyunsaturated fatty acids than to saturated fatty acids suggests another pathogenetic factor contributing to their glucose intolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Polyunsaturated fatty acids augment insulin secretion.

Carbohydrate intolerance is positively correlated with animal fat consumption and is more common in beef eating populations. In contrast, individuals consuming diets comprised of polyunsaturated fats have a lower incidence of diabetes mellitus. To test the hypothesis that dietary fats may influence carbohydrate metabolism, serum glucose, insulin, and gastric inhibitory polypeptide (GIP) responses to three mixed test meals of varying fatty acid composition were assessed in 12 normal subjects. Fatty acids in the meals were either saturated fats or polyunsaturated fats derived from vegetables or fish. Each test meal provided 40% of a subject's calculated daily caloric requirement and contained approximately 45% carbohydrate, 40% fat, and 15% protein. Serum insulin responses were 62% higher (p less than 0.01) after the fish and 39% higher (p less than 0.01) after the vegetable meals compared to the saturated fat meal. No significant differences in insulin responses were observed between the vegetable and fish meals. Serum glucose concentration was slightly higher (p less than 0.02) during the fish meal than with the vegetable or saturated fat meals. The GIP levels were comparable following the fish and vegetable meals and were 25% lower than those observed with the saturated fat meal. These findings suggest that diets enriched with polyunsaturated fatty acids augment insulin secretion significantly more than a diet comprised primarily of saturated fatty acids. The mechanism for this increased insulin secretion is unknown but did not appear to be mediated through differences in serum glucose values or through the insulin-otrophic effects of GIP.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of omega 3 fatty acids on insulin secretion and insulin sensitivity.

Carbohydrate intolerance is positively correlated with animal fat consumption and is more common in beef eating populations. In contrast, individuals consuming diets comprised of polyunsaturated fats have a lower incidence of diabetes mellitus. This is especially apparent in the Eskimos living in Alaska and Greenland whose diet is highly enriched with omega 3 fatty acids. It is hypothesized that dietary enrichment with omega 3 fatty acids increases the incorporation of these fatty acids into the beta cell phospholipid membrane thus enhancing insulin secretion. It is also proposed that similar changes occur in the phospholipid membrane composition of peripheral cells. These changes in the membrane phospholipids would then theoretically increase both insulin receptor binding affinity and sensitivity, thus enhancing glucose transport across their membranes. Augmented insulin secretion and increased insulin sensitivity induced by chronic omega 3 fatty acid ingestion would positively influence carbohydrate metabolism and improve glucose homeostasis.