Journal Watch

Prepared for IDDT by Jim Young

March 2016

Examining the “Killer K” of diabetic ketoacidosis at a tertiary care hospital
Bertha Wong et al. Canadian Journal of Diabetes. Doi:

Hypokalemia [low potassium] is a frequently cited as a complication of diabetic ketoacidosis (DKA) treatment. This study assessed the prevalence of hypokalemia and its associated factors in patients with DKA and identified opportunities to improve care. 40 cases of DKA were included in the study, and the overall prevalence of hypokalemia during DKA treatment was 38%, with 25% in type 1 and 56% in type 2 diabetes. Males were more likely to experience hypokalemia (87%), and 47% of hypokalemic incidents occurred in the first presentation of diabetes. 10 cases of significant hypokalemia were reviewed and identified 23 errors in 6 cases, of which 87% were deemed to be preventable. The most common errors were noncessation of insulin infusion during hypokalemia (60%), inadequate potassium supplementation (50%) and infrequent biochemical monitoring (50%).


The simultaneous control of hyperglycemia and GLP-1 infusion normalize endothelial function in type 1 diabetes
Antonio Ceriello et al. Diabetes Research and Clinical Practice. Doi:

In this study fifteen people with type 1 diabetes participated in three experiments: reaching and maintaining normoglycemia for 4 hours; reaching and maintaining hyperglycemia plus GLP-1 infusion for 4 hours; and reaching and maintaining normoglycemia for 4 hours with simultaneous infusion of GLP-1. It found that both normoglycemia and GLP-1 infusion restored endothelial function, however, only the combination of normoglycemia and GLP-1 was able to normalize endothelial function. But the study confirmed that long-lasting hyperglycemia in type 1 diabetes induced a permanent alteration which contributes to maintaining endothelial dysfunction even when glycemia is normalized, and that in the presence of normoglycemia, GLP-1 can contribute to normalizing endothelial function.


Children with type 2 diabetes have significantly higher lipoprotein abnormalities than those with type 1 diabetes
Lynae J. Hanks et al. Diabetes Research and Clinical Practice. Doi:

This study set out to delineate lipoprotein profile differences between children with type 1 and 2 diabetes who were overweight/obese. Data were obtained from electronic medical records of 159 patients with type 1, and 77 with type 2 diabetes, aged 12 to 19 years. It found that there were no group differences in TC, LDL, or non-HDL. Fewer subjects with type 1 diabetes had low HDL. While no difference in HbA1c level was observed between groups, HbA1c was positively correlated with TC, LDL, non-HDL, ApoB100, and LDL pattern B. In adjusted models, apoB100 and incidence of LDL pattern B were lower in subjects with type 1 diabetes. BMI was inversely correlated with HDL, HDL-2 and HDL-3. The correlation of BMI with HDL-2 and HDL-3 were attenuated when evaluating subjects by diabetes type. The conclusions were that despite there being no difference in absolute LDL levels, subjects with type 2 diabetes were more likely to have small, dense LDL particle pattern and lower total HDL, HDL-2, and HDL-3 fractions. Furthermore, coalescence of obesity, poor glycemic control and dyslipidemia, particularly in patients with type 2 diabetes, may accelerate CVD progression early in life.


Influence of initial insulin dosage on blood glucose dynamics of children and adolescents with newly diagnosed type 1 diabetes mellitus
Yi Wang   et al. Pediatric Diabetes. Doi: 10.1111/pedi.12374

This study investigated the effect of initial insulin dosage on blood glucose (BG) dynamics, β-cell protection, and oxidative stress in type 1 diabetes mellitus. Sixty patients newly diagnosed with type 1 diabetes were randomly assigned to continuous subcutaneous insulin infusions of 0.6 IU/kg/day (group 1), 1.0 IU/kg/day (group 2), or 1.4 IU/kg/day (group 3) for 3 weeks. BG was monitored continuously for the first 10 days and the last 2 days of week 2 and 3. Fasting C-peptide and HbA1c were assayed after 1, 6, and 12 months of insulin treatment. It was found that BG decreased to the target range by the end of week 3 (group 1), week 2 (group 2), or week 1 (group 3). The actual insulin dosage over the 3 weeks, frequency of hypoglycemia on week 1 and 2, and median BG at the end of week 1 differed significantly, but not the honeymoon period in the three groups. No severe hypoglycemia event was observed in any patient, but there was significant difference in the first occurrence of hypoglycemia. The authors conclude that differences in initial insulin dosage produced different BG dynamics in week 1, equivalent BG dynamics on week 2 and 3, but had no influence on short- and long-term BG control and honeymoon phase. A wide range of initial insulin dosage could be chosen if guided by BG monitoring.


Lower dose basal insulin infusion has positive effect on glycaemic control for children with type I diabetes on continuous subcutaneous insulin infusion therapy
Ron J Schulten et al. Pediatric Diabetes. Doi: 10.1111/pedi.12352

The aim of this study was to explore a possible relationship between proportion of basal insulin dose (%BD/T) and glycaemic control in children with type I diabetes on continuous subcutaneous insulin infusion (CSII) therapy. The study recruited all patients under the age of 18 with type I diabetes mellitus, treated in a general hospital in Utrecht, the Netherlands. Data from 847 outpatient visits of 78 patients [31 males and 47 females] were analysed. Patients were followed up for 29 months with an average of 10 visits. The findings were that a low dose basal insulin infusion, as a percentage of total insulin dose, had a positive effect on HbA1c-levels. A change of 10% in %BD/T results in a decrease or increase of HbA1c of 0.22%. The authors say that their findings support the tendency to aim at the lowest basal insulin requirements in pump setting strategy.


Insulin pump use compared with intravenous insulin during labour and delivery: the INSPIRED observational cohort study
E. Drever et al. Diabetic Medicine. Doi: 10.1111/dme.13106

This retrospective cohort study examined 161 consecutive pregnancies in women with Type 1 diabetic that were delivered during 2000 – 2010 at Mount Sinai Hospital, Toronto, Canada. Capillary blood glucose levels during labour and delivery and time in/out of target (target: 4–6 mmol/l) were compared along with neonatal outcomes for three groups: (1) 31 women on pumps who stayed on pumps during labour (pump/pump), (2) 25 women on pumps who switched to intravenous (IV) insulin infusion during labour (pump/IV), and (3) 105 women on multiple daily injections who switched to IV insulin infusion during labour (MDI). The study discovered that there were no significant differences between the mean or median glucose values during labour and delivery across all three groups, and no significant difference in time spent hypoglycaemic. However, women in the pump/pump group had significantly better glycaemic control as defined by mean glucose (5.5 vs. 6.4 mmol/l), median glucose (5.4 vs. 6.3 mmol/l), and more time spent in target (60.9% vs. 39.2%) compared with women in the pump/IV group. The authors posit that their study demonstrates that the continuation of CSII therapy during labour and delivery appears safe and efficacious. Moreover, women who choose to continue CSII have better glucose control during delivery than those who switch to IV insulin, suggesting that it should be standard practice to allow women the option of continuing CSII during labour and delivery.


Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus
Mattias Brunström, and Bo Carlberg. BMJ. Doi:

The investigators conducted a highly sensitive search of: CENTRAL, Medline, Embase, and BIOSIS. Forty-nine trials met the inclusion parameters for analysis, and included 73,738 participants. Most of the participants had type 2 diabetes. If baseline systolic blood pressure was greater than 150 mm Hg, antihypertensive treatment reduced the risk of all-cause mortality, cardiovascular mortality, myocardial infarction, stroke and end stage renal disease. If baseline systolic blood pressure was 140-150 mm Hg, additional treatment reduced the risk of all-cause mortality, myocardial infarction, and heart failure. If baseline systolic blood pressure was less than 140 mm Hg, however, further treatment increased the risk of cardiovascular mortality, with a tendency towards an increased risk of all-cause mortality. Further analyses showed a worse treatment effect with lower baseline systolic blood pressures for cardiovascular mortality and myocardial infarction. The conclusions were that antihypertensive treatment reduces the risk of mortality and cardiovascular morbidity in people with diabetes mellitus and a systolic blood pressure more than 140 mm Hg. If systolic blood pressure is less than 140 mm Hg, however, further treatment is associated with an increased risk of cardiovascular death, with no observed benefit.


Subcutaneous rapid-acting insulin analogues for diabetic ketoacidosis
Carlos A Andrade-Castellanos et al. Cochrane. Doi: 10.1002/14651858.CD011281.pub2

This study assessed the effects of subcutaneous rapid-acting insulin analogues for the treatment of diabetic ketoacidosis. The authors searched MEDLINE, PubMed, EMBASE, LILACS, CINAHL, and the Cochrane Library, and also the trials registers WHO ICTRP Search Portal and Two review authors independently extracted data, assessed studies for risk of bias, and evaluated overall study quality. In all five trials were included with 201 randomised participants (110 participants to subcutaneous rapid-acting insulin analogues and 91 to intravenous regular insulin). In summary the authors report that on the basis of mostly low- to very low-quality evidence that there are neither advantages nor disadvantages when comparing the effects of subcutaneous rapid-acting insulin analogues versus intravenous regular insulin for treating mild or moderate DKA.


The economic burden of post-prandial hyperglycemia (PPH) among people with Type 1 and Type 2 diabetes in three countries
Meryl Brod et al. Diabetes Therapy. Doi: 10. 1007/​s13300-016-0154-2

While the economic burden of diabetes is well studied, little is known about economic costs specific to PPH. This study investigated costs of PPH related to work, diabetes management, and use of healthcare resources among people with diabetes taking bolus insulin. Data was collected in a web survey of 906 adults with type 1 (39%) and type 2 (61%) diabetes taking bolus insulin in Germany (34%), the UK (26%), and the USA (40%). Sixty-two percent of respondents experienced PPH in the past week, and respondents averaged 1.7 episodes per week. Working respondents indicated that PPH affected their work productivity: 27% missed work time and 71% experienced work productivity issues while at work due to a recent episode of PPH. In terms of diabetes management, respondents with PPH in the past week measured their blood glucose (BG) more frequently than those without PPH. PPH was also significantly associated with greater use of healthcare resources. Compared to those without PPH, respondents with PPH reported greater contact with healthcare professionals related to diabetes in the past and were more likely to report medical complications related to diabetes. The authors posit that reducing the incidence of PPH would help mitigate costs.


Association between plasma uric acid levels and cardiorenal function in adolescents with Type 1 diabetes
Yuliya Lytvyn et al. Diabetes Care. Doi: 10.2337/dc15-2345

Because the relationship between plasma uric acid (PUA) and renal and cardiovascular parameters in adolescents with type 1 diabetes (T1D) is not well understood, this exploratory analysis looked at the association between PUA and estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (ACR), blood pressure, endothelial function, and arterial stiffness in adolescents with T1D. The findings were that even within the physiological range, PUA levels were significantly lower in T1D adolescent patients compared with healthy controls. There was an inverse relationship between PUA and eGFR, which probably reflected an increase in clearance. No associations were observed with ACR, blood pressure, arterial stiffness, or endothelial function. The authors conclude that in contrast with adults, adolescents with T1D PUA may not yet be associated with cardiorenal abnormalities.