Suboptimal Nocturnal Glucose Control Is Associated With Large for Gestational Age in Treated Gestational Diabetes Mellitus.

OBJECTIVE: Continuous glucose monitoring (CGM) provides far greater detail about fetal exposure to maternal glucose across the 24-h day. Our aim was to examine the role of temporal glucose variation on the development of large for gestational age (LGA) infants in women with treated gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: We performed a prospective observational study of 162 pregnant women with GDM in specialist multidisciplinary antenatal diabetes clinics. Participants undertook 7-day masked CGM at 30-32 weeks' gestation. Standard summary indices and glycemic variability measures of CGM were calculated. Functional data analysis was applied to determine differences in temporal glucose profiles. LGA was defined as birth weight ≥90th percentile adjusted for infant sex, gestational age, maternal BMI, ethnicity, and parity. RESULTS: Mean glucose was significantly higher in women who delivered an LGA infant (6.2 vs. 5.8 mmol/L, P = 0.025, or 111.6 mg/dL vs. 104.4 mg/dL). There were no significant differences in percentage time in, above, or below the target glucose range or in glucose variability measures (all P > 0.05). Functional data analysis revealed that the higher mean glucose was driven by a significantly higher glucose for 6 h overnight (0030-0630 h) in mothers of LGA infants (6.0 ± 1.0 mmol/L vs. 5.5 ± 0.8 mmol/L, P = 0.005, and 108.0 ± 18.0 mg/dL vs. 99.0 ± 14.4 mg/dL). CONCLUSIONS: Mothers of LGA infants run significantly higher glucose overnight compared with mothers without LGA infants. Detecting and addressing nocturnal glucose control may help to further reduce rates of LGA in women with GDM.

Impaired quality of life in patients with treated acromegaly despite long-term biochemically stable disease: Results from a 5-years prospective study.

OBJECTIVE: Patients with acromegaly demonstrate impaired quality of life (QoL), but data on long-term QoL changes in treated acromegaly are limited. This study evaluates and identifies factors that influence QoL in patients with long-term biochemical remission. DESIGN: The study consists of a cross-sectional arm comparing QoL between patients with treated and controlled acromegaly and healthy controls; and a longitudinal arm assessing QoL changes in patients with biochemically stable disease during 5.7±0.6 years of follow-up. PATIENTS: A total of 58 patients and 116 matched controls were recruited for the cross-sectional arm; 28 patients completed the longitudinal arm. MEASUREMENTS: Three generic questionnaires (Psychological General Well-Being Schedule [PGWBS], 36-item Short-Form [SF-36], EuroQoL [EQ-5D]) and the disease-specific acromegaly QoL questionnaire (AcroQoL) were applied. RESULTS: Quality of life assessment was performed 11.6±8.2 years following diagnosis and treatment of acromegaly. Patients with treated acromegaly had lower QoL scores compared with controls in all questionnaires with the exception of the PGWBS "Anxiety" subscale. The AcroQoL "Appearance" subscale and the "Physical Function" subscales of the remaining questionnaires were the most underscored domains. No difference in the total and subscale scores of all questionnaires was observed between baseline and follow-up, with the exception of the SF-36 "Physical Function," where a decline was found (58.5±24.7% vs 43.1±31.1%; P=.002). However, after adjusting for covariates, no significant change in any of the QoL scores was seen. Duration of IGF-1/GH control was positively correlated with QoL scores in most questionnaires at baseline, whereas use of GH lowering therapy at the time of QoL assessment was a negative predictive factor of QoL. CONCLUSION: Patients with biochemically controlled acromegaly demonstrate impaired QoL, which persists despite long-term disease control. This primarily consists of impaired physical function and secondly of impaired psycho-social well-being. Duration of biochemical disease control and current use of GH lowering therapy was the predominant factors determining patients' QoL.

Sympathetic activation and vasoregulation in response to carbohydrate ingestion in patients with congestive heart failure.

BACKGROUND: In normal individuals, carbohydrate ingestion increases sympathetic vasoconstrictor activity but causes net vasodilatation in the same vascular bed. This study quantified the effects of carbohydrate ingestion on muscle sympathetic nerve activity (MSNA) and vasoregulation in patients with congestive heart failure (CHF). We hypothesized that high resting levels of MSNA in patients with CHF would blunt further increases in MSNA following carbohydrate ingestion and that their sympathetic activation would restrain vasodilatation. METHODS: Eleven patients with treated severe CHF and 11 age- and body mass index-matched normal controls (NCs) were studied for 2 hours after a high-carbohydrate meal. MSNA was measured by peroneal microneurography and calf blood flow by venous occlusion plethysmography. RESULTS: Patients with CHF had higher (P < 0.03) baseline MSNA (67 ± 4.0 bursts/100 beats) than NCs (51 ± 5.8 bursts/100 beats) and lower (P < 0.001) baroreflex sensitivity (2.1 ± 0.58 ms/mm Hg) than NCs (7.4 ± 1.2 ms/mm Hg). Carbohydrate ingestion was associated with a significant increase in MSNA (P < 0.05) and calf blood flow (P < 0.01) with unchanged blood pressure in CHF patients. The magnitude of responses in CHF patients was not significantly different from that in NCs, but vasodilatation was delayed significantly (by 30 minutes). CONCLUSIONS: Despite considerable resting sympathoexcitation and reduced baroreflex sensitivity, patients with CHF exhibited further increases in MSNA after carbohydrate ingestion, achieving levels similar to those after myocardial infarction. They also had temporally delayed vasodilatation, which could contribute to cachexia and muscle weakness in CHF patients. These observations suggest that high-carbohydrate meals may adversely affect CHF patients via altered autonomic tone and blood-flow patterns.

Impact of type 2 diabetes mellitus on sympathetic neural mechanisms in hypertension.

BACKGROUND: Essential hypertension (EHT) is a major cardiovascular risk factor, and the additional presence of type 2 diabetes mellitus (DM2) increases this risk. However, although the sympathetic nerve hyperactivity of EHT is known to play a role in cardiovascular risk, the level of sympathetic nerve activity is known neither in DM2 nor in hypertensive type 2 diabetic patients (EHT+DM2). Therefore, we planned to quantify the vasoconstrictor sympathetic nerve activity in patients with EHT+DM2 and with DM2 relative to that in matched groups with EHT and normal blood pressure (NT). METHODS AND RESULTS: In 68 closely matched subjects with EHT+DM2 (n=17), DM2 (n=17), EHT (n=17), and NT (n=17), we measured resting muscle sympathetic nerve activity as the mean frequency of multiunit bursts (MSNA) and of single units (s-MSNA) with defined vasoconstrictor properties. The s-MSNA in EHT+DM2 (97+/-3.8 impulses/100 beats) was greater (at least P<0.001) than in EHT (69+/-3.4 impulses/100 beats) and DM2 (78+/-4.1 impulses/100 beats), and all these were significantly greater (at least P<0.01) than in NT (53+/-3.3 impulses/100 beats) despite similar age and body mass index. The MSNA followed a similar trend. In addition, the level of insulin was also raised in EHT+DM2 (20.4+/-3.6 microU/mL) and DM2 (18.1+/-3.1 microU/mL; at least P<0.05) compared with HT or NT. CONCLUSIONS: Patients with EHT+DM2, EHT, or DM2 had central sympathetic hyperactivity, although plasma insulin levels were raised only in EHT+DM2 and DM2. The combination of EHT and DM2 resulted in the greatest sympathetic hyperactivity and level of plasma insulin, and this hyperactivity could constitute a mechanism for the increased risks of this condition.

Sympathetic nerve hyperactivity is associated with increased peripheral vascular resistance in hypopituitary patients with growth hormone deficiency.

OBJECTIVE: Hypopituitary patients with untreated GH deficiency have increased cardiovascular mortality. Sustained vasoconstriction is an important factor in the development of hypertension and insulin resistance. This study was designed to see whether peripheral vascular resistance was increased in subjects with GH deficiency and to examine the mechanisms involved. METHODS: Nine patients with GH deficiency and nine matched control subjects were studied. Calf vascular resistance was measured by venous occlusion plethysmography and sympathetic vasoconstrictor nerve activity by peroneal microneurography. RESULTS: Subjects with GH deficiency had a significantly lower blood flow (by 31%) and higher vascular resistance (by 48%) than the control group. In addition, they had a significantly higher sympathetic vasoconstrictor activity (by 67%) and this correlated with the vascular resistance (r = 0.45; P < 0.04). CONCLUSIONS: Patients with GH deficiency have an increased peripheral vascular resistance that is contributed to by an increase in central sympathetic vasoconstrictor discharge to the peripheral vasculature. This could be important in the development of cardiovascular disease in this condition.

Carbohydrate ingestion, with transient endogenous insulinaemia, produces both sympathetic activation and vasodilatation in normal humans.

It has been shown that sustained insulin infusion causes an increase in sympathetic vasoconstrictor discharge but, despite this, also causes peripheral vasodilatation. The present study was designed to determine in healthy subjects the effect of ingestion of a carbohydrate meal, with its attendant physiological insulinaemia, on vascular resistance in and sympathetic vasoconstrictor discharge to the same vascular bed, and the relationship between these parameters. Fifteen healthy subjects were studied for 2 h following ingestion of a carbohydrate meal. Calf vascular resistance was measured by venous occlusion plethysmography, and muscle sympathetic nerve activity was assessed by peroneal microneurography. Five of the subjects also ingested water on a separate occasion, as a control. Following the carbohydrate meal, the serum insulin concentration increased to 588+/-72 pmol/l. This was associated with a 47% increase in skeletal muscle blood flow (P<0.001), a 39% fall in vascular resistance (P<0.001) and a 57% increase in sympathetic activity (P<0.001). There was a significant correlation between the increase in insulin and the changes in blood flow, vascular resistance and sympathetic activity. In conclusion, we have shown that ingestion of a carbohydrate meal, with its attendant physiological insulinaemia, was associated with overriding skeletal muscle vasodilatation, despite an increase in sympathetic vasoconstrictor discharge to the same vascular bed. These mechanisms may be important in ensuring optimal glucose uptake and maintenance of blood pressure postprandially.