Food and Agricultural Organization of the United Nations PA N I S F I A T G u id e in e s o n fo o d fo r tific atio n w th m ic r o n u tr ie n ts Interest in micronutrient malnutrition has increased greatly over the last few years. One of the main reasons is the realization that micronutrient malnutrition contributes substantially to the global burden of disease. Furthermore, although micronutrient malnutrition is more frequent and severe in the developing world and among disadvantaged populations, it also represents a public health problem in some industrialized countries. Measures to correct micronutrient deficiencies aim at ensuring consumption of a balanced diet that is adequate in every nutrient. Unfortunately, this is far from being achieved everywhere since it requires universal access to adequate food and appropriate dietary habits. Food fortification has the dual advantage of being able to deliver nutrients to large segments of the population without requiring radical changes in food consumption patterns.

Guidelines on food fortification with micronutrients

Type 2 diabetes mellitus is a chronic metabolic disorder that results from defects in both insulin secretion and insulin action. An elevated rate of basal hepatic glucose production in the presence of hyperinsulinemia is the primary cause of fasting hyperglycemia; after a meal, impaired suppression of hepatic glucose production by insulin and decreased insulin-mediated glucose uptake by muscle contribute almost equally to postprandial hyperglycemia. In the United States, five classes of oral agents, each of which works through a different mechanism of action, are currently available to improve glycemic control in patients with type 2 diabetes. The recently completed United Kingdom Prospective Diabetes Study (UKPDS) has shown that type 2 diabetes mellitus is a progressive disorder that can be treated initially with oral agent monotherapy but will eventually require the addition of other oral agents, and that in many patients, insulin therapy will be needed to achieve targeted glycemic levels. In the UKPDS, improved glycemic control, irrespective of the agent used (sulfonylureas, metformin, or insulin), decreased the incidence of microvascular complications (retinopathy, neuropathy, and nephropathy). This review examines the goals of antihyperglycemic therapy and reviews the mechanism of action, efficacy, nonglycemic benefits, cost, and safety profile of each of the five approved classes of oral agents. A rationale for the use of these oral agents as monotherapy, in combination with each other, and in combination with insulin is provided.

Pharmacologic Therapy for Type 2 Diabetes Mellitus

ContextCare of patients with type 2 diabetes has been revolutionized throughout
the past several years—first, by the realization of the importance of
tight glycemic control in forestalling complications, and second, by the availability
of several unique classes of oral antidiabetic agents. Deciphering which agent
to use in certain clinical situations is a new dilemma facing the primary
care physician.ObjectiveTo systematically review available data from the literature regarding
the efficacy of oral antidiabetic agents, both as monotherapy and in combination.Data SourcesA MEDLINE search was performed to identify all English-language reports
of unique, randomized controlled clinical trials involving recently available
oral agents for type 2 diabetes. Bibliographies were also reviewed to find
additional reports not otherwise identified.Study Selection and Data ExtractionStudies (63) were included in the analysis if they had a study period
of at least 3 months; if each group contained at least 10 subjects at the
study's conclusion; and if hemoglobin A1c was reported. When multiple
dosages of a drug were tested, the results of the highest approved dosage
were used. In placebo-controlled trials, hemoglobin A1c data are
presented as the difference between the change in treated vs placebo subjects.Data SynthesisFive distinct oral drug classes are now available for the treatment
of type 2 diabetes. Compared with placebo treatment, most of these agents
lower hemoglobin A1c levels approximately 1% to 2%. Equivalent
efficacy is usually demonstrated when different agents are compared with one
another in the same study population. When they are used in combination, there
are additional glycemic benefits. Long-term vascular risk reduction has been
demonstrated only with sulfonylureas and metformin.ConclusionsWith few exceptions, the available oral antidiabetic agents are equally
effective at lowering glucose concentrations. Their mechanisms of action are
different, however, and as a result they appear to have distinct metabolic
effects. These are reflected in their adverse effect profiles and their effect
on cardiovascular risk, which may influence drug choice.

https://jamanetwork.com/journals/jama/articlepdf/194576/JSR10000.pdf

Oral Antihyperglycemic Therapy for Type 2 Diabetes: Scientific Review

Iodine-deficiency disorders

Background Metformin is an oral anti-hyperglycemic agent that has been shown to reduce total mortality compared to other anti-hyperglycemic agents, in the treatment of type 2 diabetes mellitus. Metformin, however, is thought to increase the risk of lactic acidosis, and has been considered to be contraindicated in many chronic hypoxemic conditions that may be associated with lactic acidosis, such as cardiovascular, renal, hepatic and pulmonary disease, and advancing age. Objectives To assess the incidence of fatal and nonfatal lactic acidosis, and to evaluate blood lactate levels, for those on metformin treatment compared to placebo or non-metformin therapies. Search strategy A comprehensive search was performed of electronic databases to identify studies of metformin treatment. The search was augmented by scanning references of identified articles, and by contacting principal investigators. Selection criteria Prospective trials and observational cohort studies in patients with type 2 diabetes of least one month duration were included if they evaluated metformin, alone or in combination with other treatments, compared to placebo or any other glucose-lowering therapy. Data collection and analysis The incidence of fatal and nonfatal lactic acidosis was recorded as cases per patient-years, for metformin treatment and for non-metformin treatments. The upper limit for the true incidence of cases was calculated using Poisson statistics. In a second analysis lactate levels were measured as a net change from baseline or as mean treatment values (basal and stimulated by food or exercise) for treatment and comparison groups. The pooled results were recorded as a weighted mean difference (WMD) in mmol/L, using the fixed-effect model for continuous data. Main results Pooled data from 347 comparative trials and cohort studies revealed no cases of fatal or nonfatal lactic acidosis in 70,490 patient-years of metformin use or in 55,451 patients-years in the non-metformin group. Using Poisson statistics the upper limit for the true incidence of lactic acidosis per 100,000 patient-years was 4.3 cases in the metformin group and 5.4 cases in the non-metformin group. There was no difference in lactate levels, either as mean treatment levels or as a net change from baseline, for metformin compared to non-metformin therapies. Authors' conclusions There is no evidence from prospective comparative trials or from observational cohort studies that metformin is associated with an increased risk of lactic acidosis, or with increased levels of lactate, compared to other anti-hyperglycemic treatments.

/pdf/risk-of-fatal-and-nonfatal-lactic-acidosis-with-metformin-4ujte07kg8.pdf

Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus

OBJECTIVE: To compare the effect of repaglinide in combination with metformin with monotherapy of each drug on glycemic control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 83 patients with type 2 diabetes who had inadequate glycemic control (HbA1c > 7.1%) when receiving the antidiabetic agent metformin were enrolled in this multicenter, double-blind trial. Subjects were randomized to continue with their prestudy dose of metformin (n = 27), to continue with their prestudy dose of metformin with the addition of repaglinide (n = 27), or to receive repaglinide alone (n = 29). For patients receiving repaglinide, the optimal dose was determined during a 4- to 8-week titration and continued for a 3-month maintenance period. RESULTS: In subjects receiving combined therapy, HbA1c was reduced by 1.4 +/- 0.2%, from 8.3 to 6.9% (P = 0.0016) and fasting plasma glucose by 2.2 mmol/l (P = 0.0003). No significant changes were observed in subjects treated with either repaglinide or metformin monotherapy in HbA1c (0.4 and 0.3% decrease, respectively) or fasting plasma glucose (0.5 mmol/l increase and 0.3 mmol/l decrease respectively). Subjects receiving repaglinide either alone or in combination with metformin, had an increase in fasting levels of insulin between baseline and the end of the trial of 4.04 +/- 1.56 and 4.23 +/- 1.50 mU/l, respectively (P < 0.02). Gastrointestinal adverse events were common in the metformin group. An increase in body weight occurred in the repaglinide and combined therapy groups (2.4 +/- 0.5 and 3.0 +/- 0.5 kg, respectively; P < 0.05). CONCLUSIONS: Combined metformin and repaglinide therapy resulted in superior glycemic control compared with repaglinide or metformin monotherapy in patients with type 2 diabetes whose glycemia had not been well controlled on metformin alone. Repaglinide monotherapy was as effective as metformin monotherapy.

Effect of repaglinide addition to metformin monotherapy on glycemic control in patients with type 2 diabetes.

Clinical review 49: Iodine deficiency disorders.

Topical iodine-containing antiseptics and neonatal hypothyroidism in very-low-birthweight infants

Aims Type 2 diabetes and associated microvascular abnormalities are postulated to affect hearing. Our study reports on the relationship between Type 2 diabetes and the prevalence, 5-year incidence and progression of hearing impairment in a representative, older, Australian population.



Methods  The Blue Mountains Hearing Study is a population-based survey of age-related hearing loss conducted in a defined suburban area, west of Sydney. Hearing loss was defined as the pure-tone average of frequencies 0.5, 1.0, 2.0 and 4.0 kHz > 25 decibels hearing level (dB HL) in the better ear (bilateral hearing loss). Type 2 diabetes was defined from reported physician-diagnosed diabetes or fasting blood glucose ≥ 7.0 mmol/l.



Results  Age-related hearing loss was present in 50.0% of diabetic participants (n = 210) compared with 38.2% of non-diabetic participants (n = 1648), odds ratio (OR) 1.55 [95% confidence interval (CI) 1.11–2.17], after adjusting for multiple risk factors. A relationship of diabetes duration with hearing loss was also demonstrated. After 5 years, incident hearing loss occurred in 18.7% of participants with, and 18.0% of those without diabetes, adjusted OR 1.01 (CI 0.54–1.91). Progression of existing hearing loss (> 5 dB HL), however, was significantly greater in participants with newly diagnosed diabetes (69.6%) than in those without diabetes (47.8%) over this period, adjusted OR 2.71 (CI 1.07–6.86).



Conclusions  Type 2 diabetes was associated with prevalent, but not incident hearing loss in this older population. Accelerated hearing loss progression over 5 years was more than doubled in persons newly diagnosed with diabetes. These data explore further reported links between Type 2 diabetes and age-related hearing loss.

Relationship of Type 2 diabetes to the prevalence, incidence and progression of age-related hearing loss.

Iodine is an essential nutrient for human growth and development. The thyroid gland is dependent upon iodine for production of thyroid hormone. It is a common perception that iodine deficiency is not a major public health concern in mainland Australia, with sporadic studies carried out about a decade ago showing average urinary iodine excretion levels of around 200 µg/day. Recent evidence, however, has shown that the consumption of iodine is declining in Australia. A similar situation has occurred in the USA. The present study was designed to evaluate the urinary iodine excretion (UIE), as the indicator of iodine nutrition, in samples obtained from various demographic groups in the Sydney metropolitian area, namely: schoolchildren, healthy adult volunteers, pregnant women and patients with diabetes. Urinary iodine in spot urine sample was measured in a Technicon II autoanalyser using an in-house, semiautomated method. The results in this communication show that all four study groups had the median UIE below 100 µg/L, the criteria set by the World Health Organization for iodine repletion, and confirm what has been described previously, that iodine deficiency has reemerged in Sydney, Australia. One of the major causes of the reduced iodine intake is the reduction of iodine in milk since the dairy industry replaced iodine-rich cleaning solutions with other sanitisers. Secondly, less than 10% of the population are currently using iodised salt. A national survey into the iodine nutrition status in Australia is urgently required as part of the establishment of a systematic surveillance and legislation is required to iodise all edible salt.

/pdf/re-emergence-of-iodine-deficiency-in-australia-2t0fft8zee.pdf

Steven C Boyages

Papers

Effect of repaglinide addition to metformin monotherapy on glycemic control in patients with type 2 diabetes.

Clinical review 49: Iodine deficiency disorders.

Topical iodine-containing antiseptics and neonatal hypothyroidism in very-low-birthweight infants

Relationship of Type 2 diabetes to the prevalence, incidence and progression of age-related hearing loss.

Re-emergence of iodine deficiency in Australia.