Sex disparities in effects of cystic fibrosis-related diabetes on clinical outcomes: a matched study.

BACKGROUND: Cystic fibrosis-related diabetes (CFRD) is an increasingly prevalent comorbidity factor for patients with cystic fibrosis (CF). CFRD has been associated with an accelerated decline in clinical parameters and an increased mortality rate. OBJECTIVES: To investigate the clinical impact of CFRD on pulmonary function and clinical status using a matched study design to further explore potential causality. METHODS: Charts from the adult CF clinic at St Paul's Hospital (Vancouver, British Columbia) were retrospectively reviewed. Forty CFRD patients with and without fasting hyperglycemia were matched to CF patients with nondiabetic glucose tolerance based on sex, age and forced expiratory volume in 1 s (FEV(1)). RESULTS: Sixteen of 40 CFRD patients (40%) died compared with nine of 40 patient controls (23%) (P=0.13). CFRD patients were more likely to experience declines in FEV(1) (P<0.01), especially women (P<0.01). Patients with CFRD were not more likely to be hospitalized (P=0.39). Body mass index did not differ between groups. CONCLUSIONS: Patients with CFRD had higher rates of FEV(1) deterioration than nondiabetic patients with CF, and showed a trend toward increased mortality. The present study suggests that CFRD has a significant clinical impact and should be carefully considered when evaluating the status of CF patients.

Norepinephrine infusion during moderate-intensity exercise increases glucose production and uptake.

A role for the increase in circulating norepinephrine (NE) during intense exercise [IE; > or = 80% maximum O(2) uptake (VO(2max))] in the marked increment in glucose rate of production (Ra) during IE is hypothesized. Seven fit male subjects (27 +/- 2 yr old; body mass index, 23 +/- 1 kg/m(2); VO(2max), 63 +/- 5 mL/kg.min) underwent 40 min of postabsorptive moderate-intensity (53% VO(2max)) cycle ergometer exercise (126 +/- 14 W), once without [control (CON)] and once with NE infusion (0.1 microg/kg.min) from 30-40 min (NE). With infusion, plasma NE reached 15.9 +/- 1.0 nM (8-fold rest, 2-fold CON). Ra doubled to 4.40 +/- 0.44 in CON, but rose to 7.55 +/- 0.68 mg/kg.min with NE infusion (P = 0.003). Ra correlated strongly (r(2) = 0.92, P < 0.02) with plasma NE during and immediately after infusion. With NE infusion, peak glucose uptake [rate of disappearance (Rd), 6.57 +/- 0.59 vs. 4.53 +/- 0.55 mg/kg.min, P < 0.02] and glucose metabolic clearance rate (P < 0.05) were higher than in CON. Glycemia rose minimally during the NE infusion but did not differ between groups at any time during exercise. Glucagon-to-insulin ratio increased minimally, and epinephrine increased approximately 2.5- to 3-fold at peak but did not differ between groups. Thus, NE infusion during moderate exercise led to increments in Ra and Rd in fit individuals, supporting a possible contributory role for the increase of plasma NE in IE. NE effects on Rd and metabolic clearance rate during exercise may differ from its effects at rest.

Epinephrine infusion during moderate intensity exercise increases glucose production and uptake.

The glucoregulatory response to intense exercise [IE, >80% maximum O(2) uptake (VO(2 max))] comprises a marked increment in glucose production (R(a)) and a lesser increment in glucose uptake (R(d)), resulting in hyperglycemia. The R(a) correlates with plasma catecholamines but not with the glucagon-to-insulin (IRG/IRI) ratio. If epinephrine (Epi) infusion during moderate exercise were able to markedly stimulate R(a), this would support an important role for the catecholamines' response in IE. Seven fit male subjects (26 +/- 2 yr, body mass index 23 +/- 0.5 kg/m(2), VO(2 max) 65 +/- 5 ml x kg(-1) x min(-1)) underwent 40 min of postabsorptive cycle ergometer exercise (145 +/- 14 W) once without [control (CON)] and once with Epi infusion [EPI (0.1 microg x kg(-1) x min(-1))] from 30 to 40 min. Epi levels reached 9.4 +/- 0.8 nM (20x rest, 10x CON). R(a) increased approximately 70% to 3.75 +/- 0.53 in CON but to 8.57 +/- 0.58 mg x kg(-1) x min(-1) in EPI (P < 0.001). Increments in R(a) and Epi correlated (r(2) = 0.923, P

Glucoregulatory responses to intense exercise performed in the postprandial state.

A seven- to eightfold increment in hepatic glucose production (endogenous R(a)) occurs in postabsorptive (PA) intense exercise (IE). A similar response is likely present in the postprandial (PP) state, when most such exercise is performed, because 1) little evidence for increased intestinal absorption of glucose during exercise exists, and 2) intravenous glucose does not prevent it. We investigated IE in 10 PA and 8 PP fit, lean, young males who had exercised for 15 min at >84% maximum O(2) uptake, starting 3 h after a 412-kcal mixed meal. The meal induced a small rise in glycemia with sustained insulin and glucagon increases. Preexercise glucose total R(a) and utilization (R(d)) were equal and approximately 130% of the PA level. Exercise hyperglycemia in PP was delayed and diminished and, in early recovery, was of shorter duration and lesser magnitude (P = 0.042). Peak catecholamine (12- to 16-fold increase) and R(a) (PP: 11.5 +/- 1.4, PA: 13.8 +/- 1.4 mg. kg(-1). min(-1)) responses did not differ, and their responses during exercise were significantly correlated. Exercise glucagon, insulin, and glucagon-to-insulin responses were small or not significant. R(d) reached the same peak (PP: 8.0 +/- 0.6, PA: 9.3 +/- 0.8 mg. kg(-1). min(-1)) but was greater at 20-120 min of recovery in PP (P = 0.001). Therefore, the total R(a) response to IE is preserved despite the possibility of prior PP suppression of endogenous R(a) and is consistent with catecholamine mediation. Post-IE hyperglycemia is reduced in the postprandial state.

Gender differences in glucoregulatory responses to intense exercise.

We compared glucoregulatory responses to intense exercise (14 min at 88% maximum O(2) uptake) between genders (16 men, 12 women). Analysis of covariance of maximum O(2) uptake showed no gender effect, with 82% of variance due to fat-free mass (FFM). Glycemia rose comparably during exercise but was higher in women during recovery (P = 0.02). Glucose production [rate of appearance (R(a)); in mg/min] increased markedly in both; stepwise multiple regression and analysis of covariance of R(a) (peak and incremental area under the curve) showed no effect of gender, body weight, or FFM. Glucose uptake [rate of disappearance (R(d))] increased less than R(a) and slower in women. R(d) area under the curve related to FFM (P = 0.01) but not gender or body weight. Norepinephrine and epinephrine responses (13-18x baseline) were the same and correlated significantly with R(a). Exercise insulin and glucagon changes were slight, but postexercise hyperinsulinemia was greater in women (P = 0.018), along with higher R(d). Therefore, intense exercise glucoregulation is qualitatively similar between genders, with a "feed-forward" regulation of R(a) (consistent with catecholamine mediation). However, women have a lesser R(d) response, related to FFM. This combination leads to greater recovery-period hyperglycemia and hyperinsulinemia.

Consistent reversible elevations of serum creatinine levels in severe hypothyroidism.

BACKGROUND: Changes in routine clinical chemical indicators of renal function in the hypothyroid state are not well characterized, and are infrequently discussed in standard internal medicine or subspeciality textbooks. PATIENTS AND METHODS: We evaluated 24 consecutive patients with iatrogenic hypothyroidism induced prior to radioiodine scanning for monitoring of thyroid carcinoma. Serum creatinine and thyroid function tests were measured prior to, during, and subsequent to the period of induced hypothyroidism. RESULTS: Among 29 episodes with paired prior euthyroid and hypothyroid serum creatinine values, the hypothyroid value was greater in 26 (89.7%), and equal in 3 (10.3%), less in none; the mean hypothyroid value was significantly greater (103 vs 76 micromol/L [1.17 vs 0.87 mg/dL]) (P<.001). Among 36 episodes with paired hypothyroid and subsequent euthyroid serum creatinine values, the hypothyroid value was greater in 33 (91.7%), equal in 2 (5.6%), and less in 1 (2.8%); the mean hypothyroid value was again significantly greater (102 vs 75 pmol/L [1.15 vs 0.85 mg/dL]) (P<.001). There was no significant difference between prior and subsequent euthyroid serum creatinine values. Serum creatinine values above the stated normal range occurred in 6 of 36 hypothyroid episodes. CONCLUSIONS: There is a consistent and reversible elevation of serum creatinine values in the hypothyroid state. Frankly abnormal serum creatinine levels will occur in some cases.