Journal Watch

Prepared for IDDT by Jim Young

January 2016

Incidence and prevalence of thyroid dysfunction in type 1 diabetes
Christa Nederstigt et al. Journal of Diabetes and Its Complications. Doi:

This study estimated the prevalence and incidence of auto-immune thyroid disease(AITD) and thyroid auto-antibodies in an unselected cohort of patients with DM1. The prevalence of AITD at first screening and estimated prevalence was noted and the incidence rates were assessed during follow-up. A total of 1304 patients were included, 48.9% being female, and the mean age of diabetes onset was 18.7 years. Of all patients without known thyroid disorder first screened for AITD, 10.3 % were diagnosed with hypo- or hyperthyroidism. The average prevalence of AITD in the study population was 112/1000 patients. The researchers found 128 new cases of AITD, 101 cases of hypothyroidism and 27 of hyperthyroidism between 1995 and 2011. Age-stratified incidence of AITD was comparable at all ages, with the incidence being approximately two times higher in females. The authors conclude that the incidence of AITD among T1D patients is high, but stable among all ages and independent of diabetes duration.


Impaired awareness of hypoglycemia in adults with type 1 diabetes is not associated with autonomic dysfunction or peripheral neuropathy
Sandra E. Olsen et al. Diabetes Care. Doi: 10.2337/dc15-1469

This study asked if impaired awareness of hypoglycemia (IAH) was a risk factor for severe hypoglycemia in people with insulin-treated diabetes, and whether autonomic neuropathy was an underlying factor. Sixty-six adults with type 1 diabetes were studied, 33 with IAH and 33 with normal awareness of hypoglycemia (NAH). It was found that IAH was not associated with autonomic dysfunction or peripheral neuropathy.


The stricter the better? The relationship between targeted HbA1c values and metabolic control of pediatric type 1 diabetes mellitus
Marcin Braun et al. Journal of Diabetes Research. Doi:
Because it remains unclear how recommendations influence metabolic control of paediatric patients with type 1 diabetes mellitus, the authors of this paper compared reported HbA1c with guideline thresholds. They did this by searching MEDLINE and EMBASE for studies that reported on in children with T1DM and grouped them according to targeted obtained from regional guidelines. Discrepancies in the metabolic control between these groups were assessed by comparing the differences between actual and targeted HbA1c levels. Their study indicated that the 7.5% threshold resulted in levels being closer to the therapeutic goal, but the actual values are still higher than those observed in the “6.5%” group. They suggest that a meta-analysis of raw data from national registries or a prospective study comparing both approaches is warranted as the next step to examine this subject further.


Glucagon therapeutics, dawn of a new era for diabetes care
Jaime A. Davidson et al. Diabetes/Metabolism Research and Reviews. Doi: 10.1002/dmrr.2773

The authors state that although insulin monotherapy prevents death from ketoacidosis, it does not prevent either the hyperglycemic surges or the hypoglycemic plunges of glucose levels that plague the majority of patients with type 1 diabetes. They go on to say that significant improvements have occurred with the combination of continuous insulin delivery matched by continuous glucose monitoring, but the technology is not available for all patients, requires extensive education, is expensive and moreover, while much better than standard care, it almost never reduces HbA1c to below 6%. They posit that this may indicate that an improved diabetes therapy involving antagonism of glucagon action will for the first time control glucose levels to normal and eradicate the long-term complications of diabetes. Their caveat being that although one can never predict that results in animals will be reproduced in humans, the available evidence suggests that type 1 and type 2 diabetic patients may expect far superior control of metabolic abnormalities without the need for significant monitoring of glucose, which is a very important but expensive part of any insulin regimen.


Intranasal glucagon for treatment of insulin-induced hypoglycemia in adults with type 1 diabetes
Michael R. Rickels et al. Diabetes Care. Doi: 10.2337/dc15-1498

Treatment of severe hypoglycemia with loss of consciousness or seizure outside of the hospital setting is presently limited to intramuscular glucagon requiring reconstitution immediately prior to injection, a process prone to error or omission. In this study a needle-free intranasal glucagon preparation was compared with intramuscular glucagon for treatment of insulin-induced hypoglycemia. It was found that intranasal glucagon was highly effective in treating insulin-induced hypoglycemia in adults with type 1 diabetes. The authors assert that although the trial was conducted in a controlled setting, the results are applicable to real-world management of severe hypoglycemia, which occurs owing to excessive therapeutic insulin relative to the impaired or absent endogenous glucagon response.


HbA1c as a risk factor for severe hypoglycemia in pediatric type 1 diabetes
Beate Karges et al. Pediatric Diabetes. Doi: 10.1111/pedi.12348

This study assessed the risk of severe hypoglycemia related to HbA1c levels in a population-based cohort of pediatric type 1 diabetes patients during two time periods since 1995. Analysis was carried out of children and adolescents with type 1 diabetes from Germany and Austria between 1995–2003 (221 patients) and 2004–2012 (318 patients). It was found that rates of severe hypoglycemia and hypoglycemic coma decreased from 19.18 and 4.36 per 100 patient-years in 1995–2003 to 15.01 and 2.15 in 2004–2012, respectively. From the first to the second period, the relative risk (RR) for severe hypoglycemia and hypoglycemic coma per 1% lower HbA1c decreased from 1.22 to 1.06 and from 1.27 to 1.04, respectively. The authors conclude that in contrast to 1995–2003, low HbA1c has become a minor risk factor for severe hypoglycemia and coma in pediatric patients with type 1 diabetes in the 2004–2012 period.


New digital tool to facilitate subcutaneous insulin therapy orders: an inpatient insulin dose calculator
Marcos Tadashi Kakitani Toyoshima et al. Diabetology & Metabolic Syndrome. Doi:10.1186/s13098-015-0111-7

The authors of this paper prefixed their work with a short summary describing how inpatient hyperglycemia is associated with adverse outcomes in hospitalized patients, with or without known diabetes. The adherence to American College of Endocrinology and American Diabetes Association guidelines recommendations for inpatient glycemic control is still poor, probably because of their complexity and fear of hypoglycemia. The objective of their initiative was to create software system that could assist health care providers and hospitalists to manage the insulin therapy orders and turn them into a less complicated issue. The paper describes how they developed that software and how it could be a useful tool for all public hospitals, where generally human insulin is the only available.


Association of diabetic foot ulcer and death in a population-based cohort from the United Kingdom
J. W. Walsh et al. Diabetic Medicine. Doi: 10.1111/dme.13054

This study investigated whether the effects of diabetes-associated complications could explain the apparent relationship between diabetic foot ulcers and death. The investigators analysed data from 414,523 people with diabetes enrolled in practices associated with the Health Improvement Network in the United Kingdom. They found that 20,737 developed diabetic foot ulcers, and that 5.0% of people with new ulcers died within 12 months of their first foot ulcer visit and 42.2% of people with foot ulcers died within 5 years. After controlling for major known complications of diabetes that might influence mortality, the correlation between diabetic foot ulcers and death remained strong. The authors conclude that diabetic foot ulcers are linked to an increased risk of death, which cannot be explained by other common risk factors. So either there are major unknown risk factors associated with both diabetic foot ulcers and death, or that diabetic foot ulceration itself is a serious threat, which seems unlikely. A diabetic foot ulcer should be seen as a major warning sign for mortality, necessitating closer medical follow-up.


Increased circulating osteopontin levels in adult patients with type 1 diabetes mellitus and association with dysmetabolic profile
I Barchetta et al. European Journal of Endocrinology. Doi: 10.1530/EJE-15-0791

The introduction to this interesting paper explains that Objective Osteopontin (OPN) is a sialoprotein implicated in different immunity and metabolic pathways, playing a significant role in the development/progression of several autoimmune diseases. It was also shown that OPN participates in the acute pancreatic islets response to experimentally induced diabetes in non-obese diabetic (NOD) mice. This study enrolled 54 consecutive T1DM patients referred to a diabetes outpatient clinic at Sapienza University of Rome and 52 healthy sex and age-comparable controls. The authors say that their study demonstrates for the first time that adults with T1DM have increased serum OPN levels, and that higher OPN concentrations are associated with an unfavorable metabolic profile in these patients. No correlation was shown between OPN and HbA1c, C-peptide, insulin requirement, co-medications and diabetes duration.


Standards of Medical Care in Diabetes 2016
Diabetes Care. Doi: 10.2337/dc16-S001

This 119-page PDF provides an interesting comparison of care for diabetes in the USA (American Diabetes Association) and the UK (NICE). The United States produces annual updates whereas in the UK they are periodical. Also, it does appear that a divergence is emerging -with HbA1c targets and pharmacotherapy for example. It will be rewarding to read through this comprehensive document.