Associations between HbA1c and continuous glucose monitoring-derived glycaemic variables.

AIMS: To identify clinically useful associations between HbA1c levels and various continuous glucose monitoring-derived metrics. METHODS: We retrospectively analysed end-of-study HbA1c levels and >2 weeks of continuous glucose monitoring data collected from 530 adults with Type 1 diabetes or insulin-requiring Type 2 diabetes during four randomized trials. Each trial lasted ≥24 weeks and provided central laboratory end-of-study HbA1c levels and continuous glucose monitoring data from the preceding 3 months. Participants were assigned to groups based on either HbA1c levels or continuous glucose monitoring-derived glucose values. RESULTS: HbA1c was strongly correlated with mean glucose value (r=0.80), time spent with glucose values in the 3.9-10.0 mmol/l range (time in range; r=-0.75) and percentage of glucose values >13.9 mmol/l (r=0.72), but was weakly correlated with the percentage of glucose values <3.9 mmol/l (r=-0.39) or <3.0 mmol/l (r=-0.21). The median percentage of glucose values <3.0 mmol/l was <1.2% (<20 min/day) for all HbA1c -based groups, but the median percentage of values >13.9 mmol/l varied from 2.5% (0.6 h/day) to 27.8% (6.7 h/day) in the lowest and highest HbA1c groups, respectively. More than 90% of participants with either <2% of glucose values >13.9 mmol/l, mean glucose <7.8 mmol/l, or time in range >80% had HbA1c levels ≤53 mmol/mol (≤7.0%). For participants with HbA1c ≥64 mmol/mol (≥8.0%), the median time in range was 44%, with 90% of participants having a time in range of <59%. CONCLUSIONS: The associations shown in the present study suggest that continuous glucose monitoring-derived metrics may help guide diabetes therapy intensification efforts in an HbA1c -independent manner.

Early feeding factors associated with exclusive versus partial human milk feeding in neonates receiving intensive care.

OBJECTIVE: To evaluate early feeding factors associated with exclusive human milk (EHM) feeding at discharge in a cohort of human milk-fed infants admitted to the neonatal intensive care unit (NICU). STUDY DESIGN: Retrospective cohort of consecutively discharged infants from two NICUs over a 12-month period who received any human milk during the 24 h before hospital discharge. We used logistic regression to evaluate early feeding factors associated with EHM feeding at discharge. RESULT: We evaluated a total of 264 infants. EHM-fed infants were twice as likely to receive human milk at the first feeding compared with partial human milk-fed infants (65% vs 32%; P<0.01). In multivariable analysis, including adjustment for race and type of maternal insurance, infants receiving human milk as the initial feeding, compared with formula, had a greater odds of EHM feeding at hospital discharge (adjusted odds ratio (OR)=3.41; 95% confidence interval (CI)=1.82 to 6.39; P<0.001). CONCLUSION: Among infants admitted to the NICU whose mothers provide human milk, those receiving human milk as the first feeding were more likely to receive EHM feeding at discharge.

Plasma arginine, citrulline, and ornithine kinetics in adults, with observations on nitric oxide synthesis.

The plasma fluxes of ornithine (Orn), arginine (Arg), and citrulline (Cit) and rate of conversion of labeled ornithine-to-citrulline (QOrn-->Cit) were estimated in six healthy adult men receiving an arginine-rich or arginine-free L-amino acid-based diet, each for 6 days. On day 7 an 8-h (3-h fast, 5-h fed) primed continuous intravenous infusion of L-[guanido-15N,15N] arginine, L-[ureido-13C]citrulline, L-[5,5,2H2]ornithine, and L-[5,5,5-2H3]leucine was conducted. Mean citrulline fluxes (mumol.kg-1.h-1) were 10.4-13.6 for the various conditions and/or diets and remained unchanged (P > 0.05). Arginine flux was lowered (P < 0.01) by 38% for fed state during arginine-free period. Ornithine fluxes for arginine-rich were (P < 0.01) reduced with the arginine-free diet. Rates of QOrn-->Cit declined by 30% (P < .05) during the fed arginine-free period. Short-term restriction in the dietary supply of arginine did not alter the rate of whole body nitric oxide synthesis. One subject showed a very high output of nitrate on arginine-free diet (6 times average for remaining subjects).

Insulin decreases apical cell membrane resistance in cultured kidney cells (A6).

Intracellular potentials measured across the apical and basolateral cell membranes of cultured renal A6 cells were -53.5 +/- 1.5 and -48.7 +/- 1.3 mV, respectively, (19 measurements) and did not significantly change after insulin treatment. Analysis based on an equivalent circuit indicates that the resistances of the apical cell membrane and of the transcellular pathway decrease after insulin treatment to 36 +/- 6 and 42 +/- 6% of the control value respectively (7 measurements). Thus, the decrease in transcellular resistance which accompanies an increase in transcellular Na transport after insulin treatment appears to be connected with a commensurate decrease in apical cell membrane resistance.

Influence of extracellular Cl concentration on Cl transport across isolated skin or Rana pipiens.

The effect of changes in Cl concentration in the external and/or serosal bath on Cl transport across short-circuited frog skin was studied by measurements of transepithelial Cl influx (J13Cl) and efflux (J31Cl), short-circuit current, transepithelial potential, and conductance (Gm). J14Cl as well as J31Cl were found to have a saturating component and a component which is apparently linear with Cl concentration. The linear component of J31Cl appears only upon addition of Cl to external medium, and about 3/4 of this component does not contribute to Gm. The saturating component of J31Cl is only 5% of total J31Cl with 115mM Cl in the serosal medium. Replacement of 115 mM Cl- in external medium by SO4=, NO3-, HCO3- or I- results in 87-97% reduction of J31Cl, whereas replacement with Br- has no effect. As external Cl concentration is raised in steps from 2 to 115 mM, J13Cl and J31Cl increase by the same amount but J13Cl is persistently 0.15 mueg/cm2hr larger than J31Cl. These results indicate that at least 3/4 of linear components of J13Cl and J31Cl proceed via an exchange diffusion mechanism which seems to be located at the outer cell border. The saturating component of J13Cl is involved in active Cl transport in an inward direction, and there is evidence suggesting that Cl uptake across outer cell border, which proceeds against an electrochemical gradient, is electroneutral but not directly linked to Na.

Influence of extracellular Cl concentration on Cl transport across isolated skin of Rana pipiens.

The effect of changes in Cl concentration in the external and/or serosal bath on Cl transport across short-circuited frog skin was studied by measurements of transepithelial Cl influx (JCl13) and efflux (JCl31), short-circuit current, transepithelial potential, and conductance (Gm). JCl13 as well as JCl31 were found to have a saturating component and a component which is apparently linear with Cl concentration. The linear component of JCl31 appears only upon addition of Cl to external medium, and about 3/4 of this component does not contribute to Gm. The saturating component of JCl31 is only 5% of total JCl31 with 115 mM Cl in the serosal medium. Replacement of 115 mM Cl- in external medium by SO4=, NO3-, HCO-3 or I- results in 87-97% reduction of JCl31, whereas replacement with Br- has no effect. As external Cl concentration is raised in steps from 2 to 115 mM, JCl13 and JCl31 increase by the same amount but JCl13 is persistently 0.15 mu eq/cm2hr larger than JCl31. These results indicate that at least 3/4 of linear components of JCl13 and JCl31 proceed via an exchange diffusion mechanism which seems to be located at the outer cell border. The saturating component of JCl13 is involved in active Cl transport in an inward direction, and there is evidence suggesting that Cl uptake across outer cell border, which proceeds against an electrochemical gradient, is electroneutral but not directly linked to Na.