Effects of fish oil supplementation on glucose and lipid metabolism in NIDDM.

Fish oils, containing omega-3 fatty acids (omega 3FAs), favorably influence plasma lipoproteins in nondiabetic humans and prevent the development of insulin resistance induced by fat feeding in rats. We studied the effects of fish oils in 10 subjects (aged 42-65 yr) with mild non-insulin-dependent diabetes mellitus (NIDDM). Subjects were fed a standard diabetic diet plus 1) no supplementation (baseline), 2) 10 g fish oil concentrate (30% omega 3FAs) daily, and 3) 10 g safflower oil daily over separate 3-wk periods, the latter two supplements being given in radom order by use of a double-blind crossover design. At the end of each diet period, fasting blood glucose (FBG), insulin, and lipids were measured, and insulin sensitivity was assessed with a hyperinsulinemic-euglycemic clamp performed with [3-3H]glucose. FBG increased 14% during fish oil and 11% during safflower oil supplementation compared with baseline (P less than .05), whereas body weight, fasting serum insulin levels, and insulin sensitivity were unchanged. The absolute increase in FBG during each supplementation period correlated with the baseline FBG (fish oil, r = .83, P less than .005); safflower oil, r = .75, P = .012). Fasting plasma triglyceride levels decreased during fish oil supplementation in the 4 subjects with baseline hypertriglyceridemia (greater than 2 mM) but were not significantly reduced overall. There was no significant change in fasting plasma total, high-density lipoprotein, and low-density lipoprotein cholesterol levels. In summary, dietary fish oil supplementation adversely affected glycemic control in NIDDM subjects without producing significant beneficial effects on plasma lipids. The effect of safflower oil supplementation was not significantly different from fish oil, suggesting that the negative effects on glucose metabolism may be related to the extra energy or fat intake.(ABSTRACT TRUNCATED AT 250 WORDS)

The high-monounsaturated fat diet as a practical alternative for NIDDM.

OBJECTIVE: To examine the dietary preferences of and metabolic effects in patients with non-insulin-dependent diabetes mellitus (NIDDM) of a home-prepared high-monounsaturated fat (HM) diet compared with the recommended high-carbohydrate (CHO) diet. RESEARCH DESIGN AND METHODS: Ten men with mild NIDDM prepared HM and high-CHO diets at home alternately and in random order for 2 weeks each with a minimum 1-week washout. Before and after each diet, 24-h urine glucose, fasting lipids, fructosamine, and 6-h profiles of glucose, insulin, and triglycerides were measured. Dietary preferences were assessed by questionnaire. RESULTS: In the HM diet, patients consumed 40% of energy intake as CHO and 38% as fat (21% monounsaturated) compared with 52 and 24%, respectively, in the high-CHO diet, with equal dietary fiber content. Body weight and total energy intake were similar in both. The HM diet resulted in significantly lower 24-h urinary glucose excretion, fasting triglyceride, and mean profile glucose levels. The fructosamine levels, the fasting total, low-density lipoprotein, and high-density lipoprotein cholesterol, and the prandial triglyceride concentrations did not differ significantly as a result of the diets. The two diets did not differ in ratings for overall acceptance, taste, cost, ease of preparation, variety, or satiety. CONCLUSIONS: Prepared at home, the HM diet was, in the short-term, metabolically better in some aspects than the currently recommended diet for NIDDM. It also provided a palatable alternative.

Comparison of the effects on insulin sensitivity of high carbohydrate and high fat diets in normal subjects.

To examine whether achievable dietary changes influence insulin sensitivity, we performed euglycemic hyperinsulinemic glucose clamps in eight normal subjects who were prescribed high carbohydrate and high fat diets. The high carbohydrate diet was more than 50% (of energy intake) carbohydrate and less than 30% fat; the high fat diet was more than 45% fat (predominantly saturated) and less than 40% carbohydrate. The diets were consumed over consecutive 3-week periods in random sequence. The mean whole body glucose uptake during the glucose clamps was similar after the high carbohydrate (48.3 mumol/kg.min) and high fat diets (47.0 mumol/kg.min; P = 0.5; 95% confidence interval for the difference, -3.4 to 5.9 mumol/kg.min). Fasting blood glucose and serum insulin concentrations were also unchanged. In contrast, there were substantial effects on lipoprotein metabolism. During the high carbohydrate diet, fasting serum cholesterol decreased by 17% (P = 0.06), low density lipoprotein cholesterol decreased by 20% (P = 0.05), high density lipoprotein cholesterol decreased by 24% (P less than 0.005), and triglyceride increased by 33% (P = 0.06) compared with levels during the high fat diet. These results suggest that practically achievable high carbohydrate diets do not enhance insulin sensitivity in nondiabetic subjects and have net effects on lipoprotein metabolism that may be unfavorable.

Obstructive sleep apnea in obese noninsulin-dependent diabetic patients: effect of continuous positive airway pressure treatment on insulin responsiveness.

Patients with noninsulin-dependent diabetes mellitus (NIDDM) are often obese and frequently complain of tiredness. These features are also characteristically seen in patients with obstructive sleep apnea (OSA). Therefore, it was the aim of this study to assess the prevalence of OSA among a group of obese NIDDM patients who have some clinical features of OSA. The effect of reversal of OSA by nasal continuous positive airway pressure (CPAP) treatment on insulin responsiveness was also investigated. From a population of 179 NIDDM patients with a body mass index (BMI) greater than 35 kg/m2, we performed ambulatory sleep monitoring on 31 (15 males and 16 females) who admitted to either heavy snoring or excessive sleepiness. Results were reviewed by a sleep physician blinded to the clinical status of the patients, and 22 (70%) were found to have moderate or severe OSA, with mean oxygen desaturation indexes of 10.3 +/- 5.3 and 30.7 +/- 13.2 episodes/h, respectively. A subgroup of 10 patients (seven males and three females) with a mean BMI of 42.7 +/- 4.3 kg/m2 was treated with nightly CPAP for 4 months. These subjects all had significant OSA, with frequent obstructive apneas (mean, 47 +/- 31.6 episodes/h) and oxygen desaturation (mean minimum O2 saturation, 74 +/- 9.5%), as determined by polysomnography. One patient was excluded from analysis because of infrequent use of CPAP. Insulin responsiveness in terms of glucose disposal measured by hyperinsulinemic euglycemic clamps improved from 11.4 +/- 6.2 to 15.1 +/- 4.6 mumol/kg.min (P < 0.05) during CPAP treatment. These results indicate that OSA occurs commonly in obese NIDDM patients with excessive sleepiness or heavy snoring. Treatment of their OSA may improve insulin responsiveness.

White coat hyperglycaemia: disparity between diabetes clinic and home blood glucose concentrations.

OBJECTIVES: To identify patients with discrepantly high clinic blood glucose concentrations compared with self reported values and to assess whether such patients have errors in self monitoring technique. To determine whether, in patients with good technique, the discrepancy is a transient phenomenon related to clinic attendance. DESIGN: Prospective study of diabetes clinic patients recruited over six months. SETTING: Outpatient diabetes clinic of a teaching hospital. SUBJECTS: 34 consecutive patients with non-insulin dependent diabetes who had had at least two consecutive clinic blood glucose concentrations more than 5 mmol/l higher than the mean self reported concentration. MAIN OUTCOME MEASURES: Assessment of monitoring technique; presence of cognitive or physical impairment; serum fructosamine concentration; home and clinic blood glucose concentrations. RESULTS: 15 of 34 patients had errors in monitoring technique, 12 of whom had cognitive or physical impairment. In the remaining 19, the mean (SD) blood glucose concentrations of capillary and venous samples taken at home (10.2 (0.6) and 12.2 (1.1) mmol/l respectively) were significantly lower than in those taken at the clinic (16.8 (1.6) mmol/l, p < 0.0002). The fructosamine concentration was significantly higher in patients with monitoring errors than those without (2.4 (0.4) v 1.8 (0.4) mmol/l, p < 0.0001). CONCLUSIONS: "White coat" hyperglycaemia was detected in about half the patients but errors in technique accounted for the rest of the discrepancies. Patients' ability should be assessed before teaching self monitoring and the technique checked regularly.

Non insulin dependent diabetes mellitus. Rational approach to management.

This article emphasises the importance of the underlying insulin resistance in NIDDM and its relationship to other associated disorders. The need for screening individuals at risk, with the aim of preventing micro and macrovascular complications, is discussed. Major lifestyle changes are advocated: weight loss, exercise, cessation of smoking and reduction of alcohol intake, dietary changes and self foot care. Patient education and self monitoring of blood glucose play a part in involving the patient in his or her own management. There is much benefit to the patient from the monitoring and early treatment of blood pressure, lipid levels and any diabetic complications that develop.

Bilateral pleural effusions, ascites, and facial and peripheral oedema in a 19-year-old woman 2 weeks following commencement of insulin lispro and detemir--an unusual presentation of insulin oedema.

Insulin oedema is a rare complication of insulin therapy and usually occurs in patients with Type 1 diabetes. It can present in a variety of ways, from mild peripheral oedema to cardiac failure and massive serosal effusions. We report a 19-year-old woman with newly diagnosed Type 1 diabetes who presented with bilateral pleural effusions, ascites and extensive peripheral oedema 2 weeks after starting insulin therapy. Significant cardiac disease was excluded, and the massive fluid retention resolved spontaneously with conservative management. A review of the literature is presented.

Factors in sexual dysfunction in diabetic female volunteer subjects.

The aetiology and management of diabetic impotence is well-documented; the effects of diabetes on female sexuality are not so clear. In this study, 48 diabetic women were assessed clinically and answered detailed sexual questionnaires during a semistructured interview with a sexual counsellor. Twenty-four of the women reported one-or-more sexual dysfunctions: decreased libido, slow arousal, inadequate lubrication, anorgasmia or dyspareunia. There was no significant relationship between the presence of dysfunction and recent glycaemic control, the duration of diabetes, the presence of clinical complications or of neuropathy alone, or the attitude to sexuality. The sexual dysfunction(s) were present at the onset of diabetes in the majority of those so affected (17 of 24 patients), or were attributed to other causes in the remainder. It is suggested that sexual dysfunction in diabetic women should be treated actively as in "normal" women, since diabetes is not the major aetiological factor.

Impact of octreotide, a long-acting somatostatin analogue, on glucose tolerance and insulin sensitivity in acromegaly.

OBJECTIVE: We aimed to investigate the impact of a long-acting somatostatin analogue, octreotide, on glucose tolerance and on insulin sensitivity in acromegaly. DESIGN: We performed a non-randomized controlled trial. PATIENTS: Seven patients with active acromegaly were assessed before and during octreotide therapy given in a dose of 500 micrograms three times daily subcutaneously. MEASUREMENTS: The effects of octreotide on carbohydrate metabolism were assessed by performing a glucose tolerance test and a euglycaemic hyperinsulinaemic clamp. These latter tests were undertaken 8 hours after the last dose, allowing GH and glucagon to return to pretreatment levels during the study. RESULTS: Octreotide significantly reduced (P less than 0.05) mean +/- SEM 12-h GH (from 42 +/- 13 to 10 +/- 3 mIU/I) and IGF-I (from 4.2 +/- 0.5 to 2.1 +/- 0.5 U/ml) concentrations. Glucose tolerance was normalized in four of five patients with impaired glucose tolerance without a significant change in mean insulin concentrations. The improvement in fasting and mean blood glucose during glucose tolerance testing was dependent on the pretherapy blood glucose concentrations (r = -0.95, P = 0.002). The glucose infusion rate during the hyperinsulinaemic (5 U/h) clamp was significantly increased (P less than 0.05, 15.3 +/- 1.8 vs 24.2 +/- 5.4 mumol/kg min) following octreotide treatment. Insulin infusion during the glucose clamp completely suppressed hepatic glucose production during but not before octreotide treatment (7.9 +/- 2.4 vs 0.7 +/- 2.2 mumol/kg min, P = 0.02). Insulin-mediated stimulation of peripheral glucose uptake was unaffected by treatment. Mean GH and glucagon levels during both clamp studies were not significantly different. CONCLUSIONS: Octreotide improves whole body insulin sensitivity by an increased ability of insulin to suppress hepatic glucose production without affecting the substantial impairment of peripheral insulin action. Octreotide has beneficial effects on carbohydrate metabolism in acromegalic patients with glucose intolerance.

Meal-time intranasal insulin delivery in type 2 diabetes.

Correction of the deficiency of early meal-time insulin secretion, using intravenous insulin in patients with Type 2 diabetes causes substantial improvement in post-prandial hyperglycaemia. The present study was designed to determine whether similar benefit would result from physiological supplementation using intranasal insulin delivery. Six patients with Type 2 diabetes were studied twice during a standard mixed meal. At the start of the meal they received a single intranasal spray containing either 15 units of insulin in 1% sodium glycocholate (adjuvant agent) or glycocholate alone (placebo) in a single-blind fashion. Intranasal insulin delivery resulted in rapid absorption of insulin with peak levels (92 +/- 8 (+/- SE) mU l-1) within 5-10 min. Peak insulin levels were at least equal to those in non-diabetic subjects, though occurring at an earlier time-point. However, no significant improvement in post-prandial hyperglycaemia was seen (peak blood glucose increment 4.9 +/- 0.6 vs 5.4 +/- 0.5 mmol l-1; total 3-h response 611 +/- 53 vs 668 +/- 41 mmol l-1 min). We conclude that an elevation of insulin levels, earlier and more transient than the normal physiological response, achieved by intranasal insulin delivery at the start of a meal, fails to significantly improve the blood glucose excursion in Type 2 diabetes.

The relation between insulin sensitivity and the fatty-acid composition of skeletal-muscle phospholipids.

BACKGROUND: Insulin resistance and hyperinsulinemia are features of obesity, non-insulin-dependent diabetes mellitus, and other disorders. Skeletal muscle is a major site of insulin action, and insulin sensitivity may be related to the fatty-acid composition of the phospholipids within the muscle membranes involved in the action of insulin. METHODS: We determined the relation between the fatty-acid composition of skeletal-muscle phospholipids and insulin sensitivity in two groups of subjects. In one study, we obtained samples of the rectus abdominis muscle from 27 patients undergoing coronary artery surgery; fasting serum insulin levels provided an index of insulin sensitivity. In the second study, a biopsy of the vastus lateralis muscle was performed in 13 normal men, and insulin sensitivity was assessed by euglycemic-clamp studies. RESULTS: In the patients undergoing surgery, the fasting serum insulin concentration (a measure of insulin resistance) was negatively correlated with the percentage of individual long-chain polyunsaturated fatty acids in the phospholipid fraction of muscle, particularly arachidonic acid (r = -0.63, P < 0.001); the total percentage of C20-22 polyunsaturated fatty acids (r = -0.68, P < 0.001); the average degree of fatty-acid unsaturation (r = -0.61, P < 0.001); and the ratio of the percentage of C20:4 n-6 fatty acids to the percentage of C20:3 n-6 fatty acids (r = -0.55, P < 0.01), an index of fatty-acid desaturase activity. In the normal men, insulin sensitivity was positively correlated with the percentage of arachidonic acid in muscle (r = 0.76, P < 0.01), the total percentage of C20-22 polyunsaturated fatty acids (r = 0.76, P < 0.01), the average degree of fatty-acid unsaturation (r = 0.62, P < 0.05), and the ratio of C20:4 n-6 to C20:3 n-6 (rho = 0.76, P = 0.007). CONCLUSIONS: Decreased insulin sensitivity is associated with decreased concentrations of polyunsaturated fatty acids in skeletal-muscle phospholipids, raising the possibility that changes in the fatty-acid composition of muscles modulate the action of insulin.