Pancreatic beta-cell function dynamics in youth with GCK, HNF1A, and KCNJ11 genes mutations during mixed meal tolerance test

Objective: The aims were (1) to assess beta-cell function in GCK diabetes patients over 2-year period; (2) to evaluate the dynamics of beta-cell function in HNF1A and KCNJ11 patients after treatment optimization; using mixed meal tolerance test (MMTT) as a gold standard for non-invasive beta-cell function assessment. Research design and methods: Twenty-two GCK diabetes patients, 22 healthy subjects, 4 patients with HNF1A and 2 with KCNJ11 were recruited. Firstly, beta-cell function was compared between GCK patients versus controls; the dynamics of beta-cell function were assessed in GCK patients with two MMTTs in 2-year period. Secondly, the change of beta-cell function was evaluated in HNF1A and KCNJ11 patients after successful treatment optimization in 2-year period. Results: GCK diabetes patients had lower area under the curve (AUC) of C-peptide (CP), average CP and peak CP compared to controls. Also, higher levels of fasting, average, peak and AUC of glycemia during MMTT were found in GCK patients compared to healthy controls. No significant changes in either CP or glycemia dynamics were observed in GCK diabetes group comparing 1st and 2nd MMTTs. Patients with HNF1A and KCNJ11 diabetes had significantly improved diabetes control 2 years after the treatment was optimized (HbA1c 7.1% vs. 5.9% [54 mmol/mol vs. 41 mmol/mol], respectively, p = 0.028). Higher peak CP and lower HbA1c were found during 2nd MMTT in patients with targeted treatment compared to the 1st MMTT before the treatment change. Conclusion: In short-term perspective, GCK diabetes group revealed no deterioration of beta-cell function. Individualized treatment in monogenic diabetes showed improved beta-cell function.</p

Two strategies for response to 14 °C cold-water immersion: is there a difference in the response of motor, cognitive, immune and stress markers?

Here, we address the question of why some people have a greater chance of surviving and/or better resistance to cold-related-injuries in prolonged exposure to acute cold environments than do others, despite similar physical characteristics. The main aim of this study was to compare physiological and psychological reactions between people who exhibited fast cooling (FC; n = 20) or slow cooling (SC; n = 20) responses to cold water immersion. Individuals in whom the T(re) decreased to a set point of 35.5 °C before the end of the 170-min cooling time were indicated as the FC group; individuals in whom the T(re) did not decrease to the set point of 35.5 °C before the end of the 170-min cooling time were classified as the SC group. Cold stress was induced using intermittent immersion in bath water at 14 °C. Motor (spinal and supraspinal reflexes, voluntary and electrically induced skeletal muscle contraction force) and cognitive (executive function, short term memory, short term spatial recognition) performance, immune variables (neutrophils, leucocytes, lymphocytes, monocytes, IL-6, TNF-α), markers of hypothalamic-pituitary-adrenal axis activity (cortisol, corticosterone) and autonomic nervous system activity (epinephrine, norepinephrine) were monitored. The data obtained in this study suggest that the response of the FC group to cooling vs the SC group response was more likely an insulative-hypothermic response and that the SC vs the FC group displayed a metabolic-insulative response. The observations that an exposure time to 14 °C cold water--which was nearly twice as short (96-min vs 170-min) with a greater rectal temperature decrease (35.5 °C vs 36.2 °C) in the FC group compared with the SC group--induces similar responses of motor, cognitive, and blood stress markers were novel. The most important finding is that subjects with a lower cold-strain-index (SC group) showed stimulation of some markers of innate immunity and suppression of markers of specific immunity

Research design.

<p>BS – blood samples, T_re – rectal temperature, T_mu – muscle temperature, T_sk – skin temperature. Cognitive function (CF) testing involved the unpredictable task switching test (executive function), the forward digit-span task test (short term memory), and the forced-choice recognition memory test (short term spatial recognition). Neuromuscular (NM) testing involved evaluation of spinal (H-reflexes, M-waves) and supraspinal (V-waves) excitability, evaluation of muscle contractility characteristics induced by a 1-s electrical stimulation at 1 Hz, 20 Hz, 100 Hz and TT-100 Hz; evaluation of maximal voluntary contraction torque and central activation of exercising muscle was performed with a TT-100 Hz superimposed stimulation on the maximal voluntary contraction. Intermittent head-out immersion in bath water at 14°C continued until the rectal temperature decreased to 35.5°C or until 170 min total (120 min maximum total immersion time), at which time the immersion ended regardless of the rectal temperature.</p

VO₂, metabolic heat production and metabolic shivering before and during body cooling.

<p>*P<0.05, compared with before;</p>#<p>P<0.05 between fast cooling (FC) and slow cooling (SC) groups. Values are means ± SD.</p><p>VO₂, metabolic heat production and metabolic shivering before and during body cooling.</p

Spinal reflex excitability before and after body cooling.

<p>*P<0.05, compared with before. Fast cooling group (FC); Slow cooling group (SC). Values are means ± SD.</p><p>Spinal reflex excitability before and after body cooling.</p

Subjective sensation rating (in points) during passive body cooling.

<p>n.s. P>0.05, non-significant between fast cooling (FC) and slow cooling (SC) groups. Values are means ± SD.</p><p>Subjective sensation rating (in points) during passive body cooling.</p

The blood variables before and after body cooling.

<p>*P<0.05, compared with before;</p>#<p>P<0.05, between fast cooling (FC) and slow cooling (SC) groups. Values are means ± SD.</p><p>The blood variables before and after body cooling.</p

Changes in supraspinal (V-wave) response before and after body cooling.

<p>* P<0.05, compared with before. Fast cooling group (FC); Slow cooling group (SC).Values are means ± SD.</p

Body temperatures before and after body cooling.

<p>*P<0.05, compared with before;</p>#<p>P<0.05 between fast cooling (FC) and slow cooling (SC) groups. T_re – rectal temperature, T_mu – muscle temperature, T_sk – skin temperature. Values are means ± SD.</p><p>Body temperatures before and after body cooling.</p