Insulin inhalers don't prevent Type 1 diabetes in children with antibodies

Nasal insulin to prevent type 1 diabetes in children with HLA genotypes and autoantibodies conferring increased risk of disease: a double-blind, randomised controlled trial
Original source: The Lancet, Volume 372, Issue 9651
Authors: Kirsti Näntö-Salonen (corresponding author), Antti Kupila, Satu Simell, Heli Siljander, Tiina Salonsaari, Anne Hekkala, Sari Korhonen, Risto Erkkola, Jukka I Sipilä, Lotta Haavisto, Marja Siltala, Juhani Tuominen, Jari Hakalax, Heikki Hyöty, Jorma Ilonen, Riitta Veijola, Tuula Simell, Mikael Knip, Olli Simell
Publication date: 15 November 2008
DOI (digital document ID): 10.1016/S0140-6736(08)61309-4
Requires subscription? Yes
Publicly-available abstract: Yes

Synopsis:
In mice engineered to have risk of Type 1 diabetes, inhaled insulin has been shown to reduce their likelihood of developing diabetes. The authors wanted to know if this would work in humans. They screened a number of infants for a specific gene (the HLA-DQB1 susceptibility allele) linked to increased risk of developing Type 1 diabetes. The siblings of susceptible infants were also screened. Of these, over 11,000 infants and 1500 related siblings consented to having their children's blood screened for diabetes at 3-12 month intervals. [One would presume that for minors, their parents would have been the ones giving consent.] From these, 224 infants and 40 of their siblings (all of whom tested positive for two or more diabetes-specific antibodies) were entered into a trial in which some would be given short-acting human insulin (1 unit/kg) or placebo once a day intranasally (inhaled) until they developed Type 1 diabetes and needed traditional injectable insulin. The children were studied for an average length of 1.8 years (range lasted from 0-9.7 years). The study ended early because the insulin did not show any benefit -- as many children on insulin as on placebo developed diabetes, over similar ranges of time from the start of the trial.

Reliability:
Almost all of the authors are either medical doctors or professors of medicine. The number of children studied was not very large (only about 260), and they had already developed diabetes-related antibodies.

Would the results have been different if insulin had been administered before antibodies had developed, with the trial endpoint being the development of antibodies? Would the results have been different if a basal insulin had been used, or a different dosage?

As far as I know there is no inhaled insulin treatment for Type 1 diabetes in people. Does inhaled insulin work as primary treatment in those of that strain of mice who have developed diabetes? If it does, then the experiment is "comparing apples and oranges", and the analogous human experiment would require injected insulin.

Practical Applications:
Had there been a reduction in the number of children studied who developed Type 1 diabetes, or a significant delay in their development of Type 1 diabetes, then inhaled insulin therapy could have been used as a preventative (prophylactic) measure. The negative findings show that it cannot be.

Ethics Note:
The study was registered with ClinicalTrials.gov, number NCT00223613. Since the subjects were likely minors, their parents would have been required to provide the necessary consent.

This synopsis was based on the abstract only.

Vitamin D and Gestational Diabetes

Maternal Plasma 25-Hydroxyvitamin D Concentrations and the Risk for Gestational Diabetes Mellitus
Original source: PLoS ONE 3(11): e3753
Authors: Cuilin Zhang (corresponding author), Chunfang Qiu, Frank B. Hu, Robert M. David, Rob M. van Dam, Alexander Bralley, Michelle A. Williams
Publication date: November 18, 2008
DOI (digital document ID): 10.1371/journal.pone.0003753
Requires subscription? No
Publicly-available abstract: Yes

Synopsis:
There is increasing evidence that Vitamin D plays a role in maintaining stable blood glucose levels, but the studies directly examining circulating levels of 25-hydroxyvitamin D (25-[OH] D) are limited and inconsistent. This study aims to determine the association between levels of (25-[OH] D) earlier in pregnancy than previously examined, and the risk of the mother's developing gestational diabetes later on in the pregnancy.

A nested case-control study was conducted among 953 pregnant women. 57 had diabetes at the start of the study, and 114 women who were not diagnosed with GDM were selected as controls.

Blood samples were taken at 16 weeks gestation, with known time since last meal, and frozen at -80C until analysis. Per American Diabetes Association guidelines, participants were screened for gestational diabetes at 24-28 weeks gestation, using fasting blood glucose and an oral glucose tolerance test. The process used to measure 25-[OH] D levels produces a maximum 12% probability of error.

The results were categorized as sufficient, insufficient, or deficient.

The odds ratios were adjusted based on mother's age at conception, season of conception, diet, vitamin supplementation, mother's pre-conception body mass index, family history of Type 2 diabetes, physical activity, and whether or not the mother smoked.

The women who developed gestational diabetes tended to follow the known risk patterns: overweight, older, being non-white or Latino, and having a family history of diabetes. The heavier these women were, the lower their circulating levels of 25-[OH] D.

At 16 weeks' gestation, 25-[OH] D levels of the women who went on to develop gestational diabetes were, on average, 20% lower than those of the controls. This difference remained even when filtering out the known and suspected risk factors for diabetes. About one third of the women who developed diabetes, versus one seventh of the women who did not, had 25-[OH] D levels considered to be deficient.

Further analysis showed an inverse relationship between vitamin D levels and risk of developing gestational diabetes was observed and remained even after considering all the factors mentioned above.

Reliability:
The number of women studied was moderately large and restricted to women who sought prenatal care prior to the halfway mark in the pregnancy. The study was also limited to women who read and wrote English, and who planned to deliver at one of two study hospitals. This may or may not filter out less-affluent women in higher-risk populations.

A 12% error in the assay method may skew the results, despite statistical attempts to minimize them.

The authors submit that a single blood test for 25-[OH] D levels may not provide an accurate picture of the mother's levels of Vitamin D throughout the pregnancy; also, that some of the 25-[OH] D deficient women may have developed impaired glucose tolerance or gestational diabetes earlier in the pregnancy (but had not been screened for it). The authors would like to see a much larger study conducted to confirm (or refute) their findings.

Practical Applications:
If a firm relationship between 25-[OH] D and gestational diabetes (or diabetes in general) is confirmed, then lifestyle changes and dietary supplementation can be advised earlier in the pregnancy (or pre-pregnancy) to minimize the risks of developing gestational diabetes.

This study also contributes to the general body of research regarding Vitamin D metabolism and diabetes in general. There may be good reasons for people with diabetes, or at risk for developing diabetes, to screen for Vitamin D levels and to increase Vitamin D intake. [Please note that Vitamin D is a fat-soluble vitamin and that excess intake is not easily excreted from the body, so please consult your physician before adding additional vitamin D supplements to your diet.]


This synopsis was based on the entire article.

Diet planning as conversation, not monologue

Implementing shared decision making in nutrition clinical practice: A theory-based approach and feasibility study
Original source: Implementation Science 2008, 3:48
Authors: Sophie Desroches (corresponding author), Sylvie Tapp, Marie-Pierre Gagnon, and France Legare
Publication date: 5 November 2008
DOI (digital document ID): 10.1186/1748-5908-3-48
Requires subscription? No
Publicly-available abstract: Yes

Synopsis:
Shared decision making is one of several methods that a health professional can use to help us change our eating habits to better control diabetes and other chronic illnesses. The investigators are looking primarily at dietary approaches to lower cholesterol levels.

The traditional low-fat/low-saturated fat strategy to lower cholesterol is perceived as restrictive, leading to a tendency for people to either "cheat" or to not follow the diet at all. Recently, a number of different dietary approaches have been shown effective in lowering cholesterol -- but the variety, added to the many diet systems discussed in the popular media, can leave the general public confused. Shared decision is a method in which the dietician works collaboratively with the patient, taking into account his cultural and financial perferences, to create a healthy diet that the patient is willing to follow. The process includes explaining the best evidence of the risks and benefits of different dietary models, and explicitly states that the method does include some uncertainties.

The authors of this investigation found no formal studies supporting the use and training of a shared decision making approach using evidence-based practice, and note that some dieticians have reported difficulty in suggesting and implementing this approach.

In this paper they propose a study to learn how shared decision-making is currently used in the field of nutritional consultation, to assess dieticians' intention to adopt two specific behaviors related to shared decision making using the Theory of Planned Behavior, and to learn what the obstacles are to dieticians adopting this approach. Their proposed protocol includes the education of dieticians, the introduction of the Theory of Planned Behavior, focus group discussions in which the dieticians' views and issues are discussed, and audiotaped observation of the dieticians' interactions with patients.

The proposed research project is expected to provide preliminary data about the adoption of shared decision making by dieticians and their patients, look at dieticians' beliefs regarding their intention to adopt shared decision making behaviors and comparing their actions to their intentions, and develop questionnaires to measure this information. The researchers hope that the results generated by the proposed research project will help improve the rate at which dieticians adopt a shared decision-making approach.

Reliability:
The initial study is intended to cover only 40 dieticians, but this is considered mostly as a focus group from which the parameters of a larger study can be planned.

Practical Applications:
The end goal of this research is to increase the adoption of shared decision making in the field of nutritional consulation. Having our dieticians engage us actively, and pay attention to our input, will help us find diets we can -- and will -- live with.

This synopsis was based on the entire article.