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Objective: Insulin degludec/insulin aspart (IDegAsp) is a soluble coformulation of the novel basal analog insulin degludec (IDeg: 70%) and insulin aspart (IAsp: 30%). We compared the safety and efficacy of IDegAsp, an alternative formulation (AF) (55% IDeg and 45% IAsp), and insulin glargine (IGlar) in insulin-naïve subjects with type 2 diabetes inadequately controlled with oral antidiabetic drugs.Research Design and Methods: In this 16-week, open-label trial, subjects (mean age 59.1 years, A1C 8.5%, BMI 30.3 kg/m(2)) were randomized to once-daily IDegAsp (n = 59), AF (n = 59), or IGlar (n = 60), all in combination with metformin. Insulin was administered before the evening meal and dose-titrated to a fasting plasma glucose (FPG) target of 4.0-6.0 mmol/L.Results: After 16 weeks, mean A1C decreased in all groups to comparable levels (IDegAsp: 7.0%; AF: 7.2%; IGlar: 7.1%). A similar proportion of subjects achieved A1C <7.0% without confirmed hypoglycemia in the last 4 weeks of treatment (IDegAsp: 51%; AF: 47%; IGlar: 50%). Mean 2-h postdinner plasma glucose increase was lower for IDegAsp (0.13 mmol/L) and AF (0.24 mmol/L) than IGlar (1.63 mmol/L), whereas mean FPG was similar (IDegAsp: 6.8 mmol/L; AF: 7.4 mmol/L; IGlar: 7.0 mmol/L). Hypoglycemia rates were lower for IDegAsp and IGlar than AF (1.2, 0.7, and 2.4 events/patient year). Nocturnal hypoglycemic events occurred rarely for IDegAsp (1 event) and IGlar (3 events) compared with AF (27 events).Conclusions: In this proof-of-concept trial, once-daily IDegAsp was safe, well tolerated, and provided comparable overall glycemic control to IGlar at similar low rates of hypoglycemia, but better postdinner plasma glucose control. [ABSTRACT FROM AUTHOR]

Objective: Limited information is available regarding the metabolic effects of high altitude trekking in patients with type 2 diabetes.Research Design and Methods: Thirteen individuals with type 2 diabetes took part in a 12-day expedition to the summit of Mount Toubkal (altitude, 4,167 m), Morocco, after 6 months of exercise training. Energy expenditure, body weight, blood glucose, fasting insulin, lipids, and HbA(1c) were assessed.Results: Training reduced fasting glucose (-0.7 ± 0.9 mmol/L, P = 0.026) and increased exercise capacity (+0.3 ± 0.3 W/kg, P = 0.005). High altitude trekking decreased fasting insulin concentrations (-3.8 ± 3.2 μU/L, P = 0.04), total cholesterol (-0.7 ± 0.8 mmol/L, P = 0.008), and LDL cholesterol (-0.5 ± 0.6 mmol/L, P = 0.007).Conclusions: High altitude trekking preceded by exercise training is feasible for patients with type 2 diabetes. It improves blood glucose, lipids, and fasting insulin concentrations, while glucose control is maintained. [ABSTRACT FROM AUTHOR]

Objective: People with type 1 diabetes are at risk for developing micro- and macrovascular complications. Little is known about the gut microbiome in long-standing type 1 diabetes. We explored differences in the gut microbiome of participants with type 1 diabetes compared with healthy control subjects and associated the gut microbiome with diabetes-related complications., Research Design and Methods: Microbiome data of 238 participants with type 1 diabetes with an average disease duration of 28 ± 15 years were compared with 2,937 age-, sex-, and BMI-matched individuals. Clinical characteristics and fecal samples were collected, and metagenomic shotgun sequencing was performed. Microbial taxonomy was associated with type 1 diabetes-related characteristics and vascular complications., Results: No significant difference in the α-diversity of the gut microbiome was found between participants with type 1 diabetes and healthy control subjects. However, 43 bacterial taxa were significantly depleted in type 1 diabetes, while 37 bacterial taxa were significantly enriched. HbA1c and disease duration explained a significant part of the variation in the gut microbiome (R2 > 0.008, false discovery rate [FDR] <0.05), and HbA1c was significantly associated with the abundance of several microbial species. Additionally, both micro- and macrovascular complications explained a significant part of the variation in the gut microbiome (R2 > 0.0075, FDR < 0.05). Nephropathy was strongly associated with several microbial species. Macrovascular complications displayed similar associations with nephropathy., Conclusions: Our data show that the gut microbiome is altered in people with (long-standing) type 1 diabetes and is associated with glycemic control and diabetes-related complications. As a result of the cross-sectional design, the causality of these relationships remains to be determined., (© 2022 by the American Diabetes Association.)

Objective: Hypoglycemia poses an immediate threat for cognitive function. Due to its association with acute cognitive impairment, the International Hypoglycemia Study Group (IHSG) defines a blood glucose level <3.0 mmol/L as "level 2 hypoglycemia." In the current study we investigated whether having diabetes, type of diabetes, or hypoglycemia awareness moderates this association., Research Design and Methods: Adults with type 1 diabetes with normal (n = 26) or impaired (n = 21) hypoglycemic awareness or with insulin-treated type 2 diabetes (n = 15) and age-matched control subjects without diabetes (n = 32) underwent a hyperinsulinemic-euglycemic-hypoglycemic glucose clamp (2.80 ± 0.13 mmol/L [50.2 ± 2.3 mg/dL]). At baseline and during hypoglycemia, calculation ability, attention, working memory and cognitive flexibility were measured with the Paced Auditory Serial Addition Test (PASAT) and the Test of Attentional Performance (TAP)., Results: For the whole group, hypoglycemia decreased the mean ± SD proportion of correct answers on the PASAT by 8.4 ± 12.8%, increased reaction time on the TAP Alertness task by 32.1 ± 66.6 ms, and increased the sum of errors and omissions on the TAP Working Memory task by 2.0 ± 5.5 (all P < 0.001). Hypoglycemia-induced cognitive declines were largely irrespective of the presence or type of diabetes, level of symptomatic awareness, diabetes duration, or HbA1c., Conclusions: IHSG level 2 hypoglycemia impairs cognitive function in people with and without diabetes, irrespective of type of diabetes or hypoglycemia awareness status. These findings support the cutoff value of hypoglycemia <3.0 mmol/L (<54 mg/dL) as being clinically relevant for most people with diabetes., (© 2022 by the American Diabetes Association.)

Objective: We investigated whether serum magnesium (Mg 2+ ) was prospectively associated with macro- or microvascular complications and mediated by glycemic control (hemoglobin A 1c [HbA 1c ]), in type 2 diabetes (T2D)., Research Design and Methods: We analyzed in 4,348 participants the association of serum Mg 2+ with macrovascular disease and mortality (acute myocardial infarction [AMI], coronary heart disease [CHD], heart failure [HF], cerebrovascular accident [CVA], and peripheral arterial disease [PAD]), atrial fibrillation (AF), and microvascular complications (chronic kidney disease [CKD], diabetic retinopathy, and diabetic foot) using Cox regression, adjusted for confounders. Mediation analysis was performed to assess whether HbA 1c mediated these associations., Results: The average baseline serum Mg 2+ concentration was 0.80 ± 0.08 mmol/L. During 6.1 years of follow-up, serum Mg 2+ was inversely associated with major macrovascular, 0.87 (95% CI 0.76; 1.00); HF, 0.76 (95% CI 0.62; 0.93); and AF, 0.59 (95% CI 0.49; 0.72). Serum Mg 2+ was not associated with AMI, CHD, CVA, and PAD. During 5.1 years of follow-up, serum Mg 2+ was inversely associated with overall microvascular events, 0.85 (95% CI 0.78; 0.91); 0.89 (95% CI 0.82; 0.96) for CKD, 0.77 (95% CI 0.61; 0.98) for diabetic retinopathy, and 0.85 (95% CI 0.78; 0.92) for diabetic foot. HbA 1c mediated the associations of serum Mg 2+ with HF, overall microvascular events, diabetic retinopathy, and diabetic foot., Conclusions: Serum Mg 2+ concentration is inversely associated with the risk to develop HF and AF and with the occurrence of CKD, diabetic retinopathy, and foot complications in T2D. Glycemic control partially mediated the association of serum Mg 2+ with HF and microvascular complications., (© 2021 by the American Diabetes Association.)

Objective: Diabetes distress among patients from ethnic minorities is still poorly understood. We investigated the association between ethnicity and diabetes distress among ethnic minority groups of people with type 2 diabetes in the Netherlands, focusing on the possible effects of glycemic control, lifestyle factors, cardiovascular risk factors, and diabetes complications., Research Design and Methods: Cross-sectional data from the Dutch Diabetes Pearl cohort included people with type 2 diabetes from primary, secondary, and tertiary diabetes care programs. We used the 20-item Problem Areas in Diabetes Survey (PAID) scale to assess diabetes distress; a score ≥40 is considered to represent high distress. Ethnicity was estimated on the basis of country of birth. Sociodemographic and lifestyle data were self-reported; cardiovascular and metabolic data were retrieved from medical charts. Logistic regression analysis determined the association between ethnicity and diabetes distress, with Caucasians as the reference group., Results: Diabetes distress scores and ethnicity were available for 4,191 people with type 2 diabetes: 3,684 were Caucasian, 83 were Asian, 51 were Moroccan, 92 were African, 134 were Latin American, 46 were Turkish, and 101 were Hindustani-Surinamese. Overall, participants in minority groups had worse health outcomes than those of Caucasian descent, and diabetes distress was more prevalent (ranging from 9.6 to 31.7%, compared with 5.8% among Caucasians), even after adjusting for age, sex, education level, alcohol use, smoking, BMI, lipid profile, HbA 1c , medication use, and the presence of diabetes complications., Conclusions: Among people with type 2 diabetes in the Netherlands, ethnicity is independently associated with high diabetes distress. Further research is warranted to explain the higher prevalence of diabetes distress in minority groups and to develop effective interventions., (© 2018 by the American Diabetes Association.)

Objective: The determinants of insulin-associated weight gain in type 2 diabetes mellitus (T2DM) are partly unknown. Therefore, we conducted a prospective study to identify predictors of insulin-associated weight gain., Research Design and Methods: In patients with T2DM, we assessed physical activity by accelerometry and measured diabetes-related distress by questionnaires before and 6 and 12 months after starting insulin therapy. Glycemic control (HbA1c) and insulin dose were monitored., Results: After 12 months of insulin therapy, mean body weight had increased by 3.0 ± 2.5 kg (P < 0.001). The drop in HbA1c was correlated with insulin-associated weight gain. With the use of a multiple linear regression model, a cluster of variables was identified that significantly related to weight gain. Diabetes-related distress, initial insulin dose, and the increase of insulin dose during the course of the study as well as age appeared to be important predictors of weight gain after initiation of insulin therapy. Physical activity (measured as MET) decreased from 1.40 ± 0.04 at baseline to 1.32 ± 0.04 MET (P < 0.05) but was not significantly related to weight changes., Conclusions: Diabetes-related distress, initial and titration of insulin dose, and age all significantly predict insulin-associated weight gain. After the initiation of insulin therapy, physical activity decreased significantly, but this did not determine weight gain over the first 12 months. Our study findings may have clinical implications., (© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Background: A growing number of subjects with diabetes take part in physical activities at altitude such as skiing, climbing, and trekking. Exercise under conditions of hypobaric hypoxia poses some unique challenges on subjects with diabetes, and the presence of diabetes can complicate safe and successful participation in mountain activities. Among others, altitude can alter glucoregulation. Furthermore, cold temperatures and altitude can complicate accurate reading of glucose monitoring equipment and storage of insulin. These factors potentially lead to dangerous hyperglycemia or hypoglycemia. Over the last years, more information has become available on this subject., Purpose: To provide an up-to-date overview of the pathophysiological changes during physical activity at altitude and the potential problems related to diabetes, including the use of (continuous) blood glucose monitors and insulin pumps. To propose practical recommendations for preparations and travel to altitude for subjects with diabetes., Data Sources and Synthesis: We researched PubMed, medical textbooks, and related Internet sites, and extracted human studies and data based on relevance for diabetes, exercise, and altitude., Limitations: Given the paucity of controlled trials regarding diabetes and altitude, we composed a narrative review and filled in areas lacking diabetes-specific studies with data obtained from nondiabetic subjects., Conclusions: Subjects with diabetes can take part in activities at high, and even extreme, altitude. However, careful assessment of diabetes-related complications, optimal preparation, and adequate knowledge of glycemic regulation at altitude and altitude-related complications is needed., (© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

OBJECTIVE Fatigue is a classical symptom of hyperglycemia, but the relationship between chronic fatigue and diabetes has not been systematically studied. We investigated prevalence, impact, and potential determinants of chronic fatigue in patients with type 1 diabetes mellitus (T1DM). RESEARCH DESIGN AND METHODS Out of 324 randomly selected T1DM outpatients, 214 participated in this cross-sectional observational study. Participants were compared with age- and sex-matched population-based controls. Chronic fatigue, functional impairments, current health status, comorbidity, diabetes-related factors, and fatigue-related cognitions and behaviors were assessed with questionnaires, and HbA1c values and comorbidity were assessed with medical records. Sixty-six patients underwent continuous glucose monitoring combined with an electronic fatigue diary for 5 days. Acute fatigue and four glucose parameters were determined: mean, variability, and relative time spent in hypoglycemia and hyperglycemia. RESULTS T1DM patients were significantly more often chronically fatigued (40%; 95% CI 34-47%) compared with matched controls (7%; 95% CI 3-10%; P < 0.001). Chronically fatigued patients had significantly more functional impairments. Fatigue was the most troublesome symptom. Age, depression, pain, sleeping problems, low self-efficacy concerning fatigue, and physical inactivity were significantly associated with chronic fatigue. Chronically fatigued patients spent slightly less time in hypoglycemia (proportion 0.07 ± 0.06 vs. 0.12 ± 0.10; P = 0.025). Glucose parameters were not related to acute fatigue. CONCLUSIONS Chronic fatigue is highly prevalent and clinically relevant in T1DM. Its significant relationship with cognitive behavioral variables and weak association with blood glucose levels suggests that behavioral interventions could be helpful in managing chronic fatigue in T1DM.

Objective: Clamp studies have shown that the absorption and action of rapid-acting insulin are faster with injection by a jet injector than with administration by conventional pen. To determine whether these pharmacokinetic changes also exist in patients with diabetes and benefit postprandial glucose control, we compared the pharmacologic profiles of insulin administration by jet injection versus conventional insulin pen after a standardized meal in patients with type 1 or type 2 diabetes., Research Design and Methods: In a randomized, double-blind, double-dummy crossover study, 12 patients with type 1 diabetes and 12 patients with type 2 diabetes received insulin aspart either by jet injection or by conventional pen, in both cases followed by a standardized meal. Blood was sampled for 6 h for determination of glucose and insulin levels to calculate pharmacologic profiles., Results: Insulin administration by jet injection resulted in shorter time until peak plasma insulin level (51.3 ± 6.4 vs. 91.9 ± 10.2 min; P = 0.003) and reduced hyperglycemic burden during the first hour (154.3 ± 20.8 vs. 196.3 ± 18.4 mmol · min · L(-1); P = 0.041) compared with conventional administration. Jet injection did not, however, significantly reduce the hyperglycemic burden during the 5-h period thereafter. There was no indication that the jet injector performed differently in patients with type 1 and type 2 diabetes., Conclusions: The considerably more rapid insulin absorption after administration by jet injector translated to a significant if modest decrease in postprandial hyperglycemia in patients with type 1 and type 2 diabetes. The improved early postprandial glucose control may specifically benefit patients who have difficulty in limiting postprandial glucose excursions.

Objective: To investigate whether the dipeptidyl peptidase-4 inhibitor vildagliptin improves endothelium-dependent vasodilatation in patients with type 2 diabetes., Research Design and Methods: Sixteen subjects with type 2 diabetes (age 59.8 ± 6.8 years, BMI 29.1 ± 4.8 kg/m(2), HbA(1c) 6.97 ± 0.61) on oral blood glucose-lowering treatment were included. Participants received vildagliptin 50 mg b.i.d. or acarbose 100 mg t.i.d. for four consecutive weeks in a randomized, double-blind, cross-over design. At the end of each treatment period, we measured forearm vasodilator responses to intra-arterially administered acetylcholine (endothelium-dependent vasodilator) and sodium nitroprusside (endothelium-independent vasodilator)., Results: Infusion of acetylcholine induced a dose-dependent increase in forearm blood flow in the experimental arm, which was higher during vildagliptin (3.1 ± 0.7, 7.9 ± 1.1, and 12.6 ± 1.4 mL ⋅ dL(-1) ⋅ min(-1) in response to three increasing dosages of acetylcholine) than during acarbose (2.0 ± 0.7, 5.0 ± 1.2, and 11.7 ± 1.6 mL ⋅ dL(-1) ⋅ min(-1), respectively; P = 0.01 by two-way ANOVA). Treatment with vildagliptin did not significantly change the vascular responses to sodium nitroprusside., Conclusions: Four weeks' treatment with vildagliptin improves endothelium-dependent vasodilatation in subjects with type 2 diabetes. This observation might have favorable cardiovascular implications.

Objective: Insulin administered by jet injectors is dispensed over a larger subcutaneous area than insulin injected with a syringe, which may facilitate a more rapid absorption. This study compared the pharmacologic profile of administration of insulin aspart by jet injection to that by conventional insulin pen., Research Design and Methods: Euglycemic glucose clamp tests were performed in 18 healthy volunteers after subcutaneous administration of 0.2 units/kg body wt of aspart, either administered by jet injection or by conventional pen, using a randomized, double-blind, double-dummy, cross over study design. Pharmacodynamic and pharmacokinetic profiles were derived from the glucose infusion rate (GIR) needed to maintain euglycemia and from plasma insulin levels, respectively., Results: The time to maximal GIR was significantly shorter when insulin was injected with the jet injector compared with conventional pen administration (51 ± 3 vs. 105 ± 11 min, P < 0.0001). The time to peak insulin concentration was similarly reduced (31 ± 3 vs. 64 ± 6 min, P < 0.0001) and peak insulin concentrations were increased (108 ± 13 vs. 79 ± 7 mU/L, P = 0.01) when insulin was injected by jet injection compared with conventional pen injection. Jet injector insulin administration reduced the time to 50% glucose disposal by ∼40 min (P < 0.0001). There were no differences in maximal GIR, total insulin absorption, or total insulin action between the two devices., Conclusions: Administration of insulin aspart by jet injection enhances insulin absorption and reduces the duration of glucose-lowering action. This profile resembles more closely the pattern of endogenous insulin secretion and may help to achieve better meal insulin coverage and correction of postprandial glucose excursions.

Objective: Safe, very high altitude trekking in subjects with type 1 diabetes requires understanding of glucose regulation at high altitude. We investigated insulin requirements, energy expenditure, and glucose levels at very high altitude in relation to acute mountain sickness (AMS) symptoms in individuals with type 1 diabetes., Research Design and Methods: Eight individuals with complication-free type 1 diabetes took part in a 14-day expedition to Mount Meru (4,562 m) and Mount Kilimanjaro (5,895 m) in Tanzania. Daily insulin doses, glucose levels, energy expenditure, and AMS symptoms were determined. Also, energy expenditure and AMS symptoms were compared with a healthy control group., Results: We found a positive relation between AMS symptoms and insulin requirements (r = 0.78; P = 0.041) and AMS symptoms and glucose levels (r = 0.86; P = 0.014) for Mount Kilimanjaro. Compared with sea level, insulin doses tended to decrease by 14.2% (19.7) (median [interquartile range]) (P = 0.41), whereas glucose levels remained stable up to 5,000 m altitude. However, at altitudes >5,000 m, insulin dose was unchanged (36.8 ± 17 vs. 37.6 ± 19.1 international units [mean ± SD] P = 0.75), but glucose levels (7.5 ± 0.6 vs. 9.5 ± 0.8 mmol/L [mean ± SD] P = 0.067) and AMS scores (1.3 ± 1.6 vs. 4.4 ± 4 points [mean ± SD] P = 0.091) tended to increase. Energy expenditure and AMS symptoms were comparable in both groups (P = 0.84)., Conclusions: Our data indicate that in complication-free individuals with type 1 diabetes, insulin requirements tend to increase during altitudes above 5,000 m despite high energy expenditure. This change may be explained, at least partly, by AMS.

Objective: The use of thiazolidinedione (TZD) derivatives is associated with fluid retention, especially when combined with insulin. Because TZDs improve the metabolic effect of insulin, they may also reverse the blunted vascular response to insulin. We hypothesize that improvement of the action of insulin on vascular tone or permeability is the key mechanism of TZD-related fluid retention., Research Design and Methods: In a randomized, double-blind, placebo-controlled, cross-over study in 18 obese, nondiabetic subjects with features of the metabolic syndrome, we investigated the effects of a 12-week treatment with 4 mg rosiglitazone twice a day on glucose disposal, hemodynamics (including forearm vasoconstrictor response to nitric oxide [NO]), synthase inhibition by N-monomethyl-L-arginine-acetate (L-NMMA), vascular permeability (transcapillary escape rate of albumin), and plasma volume during a hyperinsulinemic-euglycemic clamp (120 min, 120 mU/m(2) per min)., Results: As expected, rosiglitazone increased the glucose infusion rate during clamping. However, neither vascular permeability nor forearm blood flow response to hyperinsulinemia or L-NMMA was affected by rosiglitazone. Compared with placebo, rosiglitazone decreased diastolic blood pressure by 5 mmHg (95% CI 2.35-6.87, P = 0.0005) and increased plasma volume by 255 ml/1.73 m(2) (80-430, P = 0.007). Interestingly, the positive effect of rosiglitazone on glucose disposal correlated with change in foot volume (R(2) = 0.53, P = 0.001)., Conclusions: Rosiglitazone improved insulin sensitivity but had no effect on NO-dependent vasodilatation in the forearm or vascular permeability in obese, insulin-resistant, nondiabetic subjects. As such, TZD-related fluid retention was not caused by improvement of the vascular actions of insulin. Nonetheless, rosiglitazone-induced improvement in insulin sensitivity appears to be correlated to edema formation.

Objective: Caffeine is a central stimulant that increases the release of catecholamines. As a component of popular beverages, caffeine is widely used around the world. Its pharmacological effects are predominantly due to adenosine receptor antagonism and include release of catecholamines. We hypothesized that caffeine reduces insulin sensitivity, either due to catecholamines and/or as a result of blocking adenosine-mediated stimulation of peripheral glucose uptake., Research Design and Methods: Hyperinsulinemic-euglycemic glucose clamps were used to assess insulin sensitivity. Caffeine or placebo was administered intravenously to 12 healthy volunteers in a randomized, double-blind, crossover design. Measurements included plasma levels of insulin, catecholamines, free fatty acids (FFAs), and hemodynamic parameters. Insulin sensitivity was calculated as whole-body glucose uptake corrected for the insulin concentration. In a second study, the adenosine reuptake inhibitor dipyridamole was tested using an identical protocol in 10 healthy subjects., Results: Caffeine decreased insulin sensitivity by 15% (P < 0.05 vs. placebo). After caffeine administration, plasma FFAs increased (P < 0.05) and remained higher than during placebo. Plasma epinephrine increased fivefold (P < 0.0005), and smaller increases were recorded in plasma norepinephrine (P < 0.02) and blood pressure (P < 0.001). Dipyridamole did not alter insulin sensitivity and only increased plasma norepinephrine (P < 0.01)., Conclusions: Caffeine can decrease insulin sensitivity in healthy humans, possibly as a result of elevated plasma epinephrine levels. Because dipyridamole did not affect glucose uptake, peripheral adenosine receptor antagonism does not appear to contribute to this effect.

Objective: Insulin resistance is associated with a predominance of small, atherogenic LDL particles that are more prone to oxidative modification. Treatment with the insulin-sensitizer troglitazone may improve LDL composition and resistance to oxidation., Research Design and Methods: In a randomized double-blind crossover design, 15 obese subjects were treated with either 400 mg troglitazone daily or placebo for 8 weeks. Insulin sensitivity (clamp), (apo)lipoproteins, LDL subclass pattern, plasma TBARS, and ex vivo LDL oxidation were determined., Results: Troglitazone treatment improved insulin sensitivity. LDL cholesterol increased from 2.58 +/- 0.18 to 2.77 +/- 0.20 mmol/l (P = 0.03) because of an increase in large (buoyant) LDL1 (from 0.45 +/- 0.04 to 0.62 +/- 0.09 mmol/l, P = 0.008). Because small (dense) LDL3 decreased, LDL1:LDL3 ratio increased (P = 0.02). Plasma TBARS concentration declined significantly, and the lag time of ex vivo LDL oxidation showed a small but significant increase., Conclusions: In obese subjects, treatment with troglitazone improves insulin sensitivity, increases the ratio of large buoyant to small dense LDL, and appears to enhance the resistance of the LDL particle to oxidation. These qualitative changes in lipoproteins may have a beneficial effect on cardiovascular risk profile and compensate for a small increase in LDL cholesterol.

Regular measurement of HbA1c (percentage) is an essential component of modern diabetes care. Factors that affect the life span of erythrocytes will also influence HbA1c results. In this study, we describe two patients with IDDM, whose regularly determined HbA1c values were considerably decreased with the concomitant use of two related sulfonamide drugs, sulfasalazine and dapsone. The fall in HbA1c results is explained by increased erythrocytopoiesis as a product of drug-induced hemolysis. Fructosamine concentrations are not affected by hemolysis and reflected glycemic control better. We conclude that under conditions of persistent (subclinical) hemolysis, as occurs during the use of sulfonamides, HbA1c is not a reliable indicator of glycemic control.