Self-reported functioning among patients with ultra-rare nemaline myopathy or a related disorder in Finland: a pilot study.

BACKGROUND: Nemaline myopathy (NM) and related disorders (NMr) form a heterogenous group of ultra-rare (1:50,000 live births or less) congenital muscle disorders. To elucidate the self-reported physical, psychological, and social functioning in the daily lives of adult persons with congenital muscle disorders, we designed a survey using items primarily from the Patient Reported Outcomes Measurement Information System, PROMIS®, and conducted a pilot study in patients with NM and NMr in Finland. The items were linked to International Classification of Functioning, Disability and Health (ICF) categories. RESULTS: In total, 20 (62.5%) out of 32 invited persons resident in Finland participated in the study; 12 had NM and 8 NMr, 15 were women and 5 men aged 19-75 years. Sixteen (80%) were ambulatory and 4 (20%) NM patients used wheelchairs. The results from the PROMIS measuring system and ICF categories both indicated that non-ambulatory patients of this study faced more challenges in all areas of functioning than ambulatory ones, but the differences were smaller in the domains measuring psychological and social functioning than in physical functioning. In addition, the COVID-19 pandemic adversely affected the functioning of non-ambulatory patients more than that of ambulatory patients. The interindividual differences were, however, noticeable. CONCLUSIONS: To our knowledge, this pilot study is the first comprehensive survey-based study of the physical, psychological, and social functioning of adult persons with nemaline myopathy or related disorders. The results indicate vulnerability of non-ambulatory patients being at higher risk to a decrease in general functioning during global or national exceptional periods. The responses also gave directions for modifying and improving the survey for future studies.

Beneficial Effects of Ketogenic Diet on Phosphofructokinase Deficiency (Glycogen Storage Disease Type VII).

Background: A deficiency of muscle phosphofructokinase (PFKM) causes a rare metabolic muscle disease, the Tarui disease (Glycogen storage disease type VII, GSD VII) characterized by exercise intolerance with myalgia due to an inability to use glucose as an energy resource. No medical treatment for GSD VII currently exists. The aim of this study was to determine whether a dietary intervention with excessive fat intake would benefit GSD VII. Patient and Methods: A ketogenic diet (KD) intervention implemented as a modified Atkins diet was established for one patient with PFKM deficiency, with a low late lactate response and very high ammonia levels associated with exercise. We recorded the KD intervention for a total of 5 years with clinical and physiotherapeutic evaluations and regular laboratory parameters. Cardiopulmonary exercise testing, including breath gas analysis and venous lactate and ammonia measurements, was performed before KD and at 3, 8 months and 5 years after initiation of KD. Results: During the 5 years on KD, the patient's muscle symptoms had alleviated and exercise tolerance had improved. In exercise testing, venous ammonia had normalized, the lactate profile remained similar, but oxygen uptake and mechanical efficiency had increased and parameters showing ventilation had improved. Conclusions: This study is the first to show a long-term effect of KD in GSD VII with an alleviation of muscle symptoms, beneficial effects on breathing, and improvement in exercise performance and oxygen uptake. Based on these findings, KD can be recommended under medical and nutritional supervision for selected patients with GSD VII, although further research of this rare disease is warranted.

Insulin-like growth factor I, binding proteins -1 and -3, risk of type 2 diabetes and macronutrient intakes in men.

The insulin-like growth factor (IGF) axis may be involved in the development of type 2 diabetes. We examined the associations of IGF-I and IGF binding proteins (IGFBP)-1 and -3 with diabetes risk and evaluated macronutrient intakes related to the observed associations. In a nested case-control study of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish male smokers aged 50-69 years, the IGF variables were measured from baseline serum samples for a random sample of 310 men with diabetes diagnosed during a 12-year follow-up and for 310 controls matched by age, recruitment day and intervention group. Diet at baseline was assessed using a validated FFQ. The associations of IGF proteins with diabetes risk were estimated using conditional logistic regression and the associations with macronutrient intakes using linear regression. IGF-I and IGFBP-3 were not associated with the incidence of diabetes. Higher IGFBP-1 was associated with lower diabetes risk in an unadjusted crude model (OR 0·25; 95 % CI 0·15, 0·42 in the highest quartile compared with the lowest), but not after adjustment for BMI (corresponding OR 0·76; 95 % CI 0·41, 1·40). Intakes of carbohydrates, plant protein and milk protein associated positively and intake of meat protein and fat negatively with IGFBP-1 (P<0·005). IGFBP-1 was inversely associated with diabetes risk, but the association was substantially dependent on BMI. The associations between macronutrient intakes and IGFBP-1 may reflect influences of nutrients or foods on insulin concentrations.

Naturally occurring and added sugar in relation to macronutrient intake and food consumption: results from a population-based study in adults.

Associations between sugar intake and the remaining diet are poorly described in modern food environments. We aimed at exploring associations of high naturally occurring and added sugar intakes with sociodemographic characteristics, intake of macronutrients, fibre and selected food groups. Our data comprised 4842 Finnish adults aged 25-74 years, who participated in the population-based DIetary, Lifestyle and Genetic determinants of Obesity and Metabolic syndrome (DILGOM) study. Diet was assessed by a validated 131-item FFQ. The food item disaggregation approach was used to estimate sucrose and fructose intakes from natural sources (naturally occurring sugar) and all other sources (added sugar). Sex-specific trends in macronutrient, fibre and food group intakes across sugar type quartiles were determined with general linear modelling adjusting for age, energy intake, leisure-time physical activity, smoking, education and BMI. Overall, results were similar across sexes. Young age was found to be a determinant of higher added sugar and lower naturally occurring sugar intakes (P < 0·0001). High added sugar intake was associated with low fibre intake (P < 0·0001) accompanied with lower fruit (P < 0·0001 women; P = 0·022 men) and vegetable consumption (P < 0·0001) and higher wheat consumption (P = 0·0003 women; P < 0·0001 men). Opposite results were found for naturally occurring sugar. Butter consumption increased by 28-32 % (P < 0·0001) when shifting from the lowest to the highest added sugar intake quartile, while a decrease of 26-38 % (P < 0·0001) was found for naturally occurring sugar. Therefore, the associations of sugar types with dietary carbohydrate and fat quality seem opposing. Proper adjustments with dietary variables are needed when studying independent relationships between sugar and health.

Unique Exercise Lactate Profile in Muscle Phosphofructokinase Deficiency (Tarui Disease); Difference Compared with McArdle Disease.

INTRODUCTION: Glycogen storage disease V (GSDV, McArdle disease) and GSDVII (Tarui disease) are the most common of the rare disorders of glycogen metabolism. Both are associated with low lactate levels on exercise. Our aim was to find out whether lactate response associated with exercise testing could distinguish between these disorders. METHODS: Two siblings with Tarui disease, two patients with McArdle disease and eight healthy controls were tested on spiroergometric exercise tests with follow-up of venous lactate and ammonia. RESULTS: A late increase of lactate about three times the basal level was seen 10-30 min after exercise in patients with Tarui disease being higher than in McArdle disease and lower than in the controls. Ammonia was increased in Tarui disease. DISCUSSION: Our results suggest that follow-up of lactate associated with exercise testing can be utilized in diagnostics to distinguish between different GSD diseases.

Glycaemic index, carbohydrate substitution for fat and risk of CHD in men.

We have examined the associations between dietary glycaemic index (GI), substitutions of total, low-, medium- and high-GI carbohydrates for fat and the risk of CHD. The study consisted of 21 955 male smokers, aged 50-69 years, within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The diet was assessed at baseline using a validated FFQ. During a 19-year follow-up, 4379 CHD cases (2377 non-fatal myocardial infarctions and 2002 CHD deaths) were identified from national registers. Relative risks (RR) and CI for CHD were analysed using Cox proportional hazards modelling, and multivariate nutrient density models were applied to examine the associations between the substitutions of macronutrients and the risk of CHD. Dietary GI was inversely associated with CHD risk: multivariate RR in the highest v. lowest quintile was 0·89 (95 % CI 0·81, 0·99). Replacement of higher-GI carbohydrates with lower-GI carbohydrates did not associate with the risk. Replacing saturated and trans-fatty acids with carbohydrates was associated with decreased CHD risk: RR for substitution of 2 % of energy intake was 0·97 (95 % CI 0·94, 0·99). On the contrary, replacing MUFA with carbohydrates was associated with an increased risk: RR for substitution of 2 % of energy intake was 1·08 (95 % CI 1·01, 1·16). We conclude that in the present study population, contrary to the hypothesis, a lower GI does not associate with a decreased risk of CHD. The associations of carbohydrates with CHD risk depend on the fatty acid composition of the diet.

Relative validity of a FFQ in measuring carbohydrate fractions, dietary glycaemic index and load: exploring the effects of subject characteristics.

FFQ require validation as part of epidemiological research of diet-disease relationships. Studies exploring associations between carbohydrate type and chronic diseases are rapidly increasing, but information on the validity of carbohydrate fractions, dietary glycaemic index (GI) and the glycaemic load (GL) estimated by FFQ is scarce. Likewise, the effects of subject characteristics on FFQ validity have been poorly documented. The present study evaluates the relative validity of an 131-item FFQ in relation to two 3 d food records (FR) performed 6 months apart focusing on the intake of carbohydrate fractions, dietary GI and the GL. Furthermore, we assessed the extent to which subjects' age, education and BMI explain differences between these methods. The study sample comprised 218 men and 292 women aged 25-74 years participating in a large population-based survey in Finland. Energy-adjusted Spearman's rank correlations ranged from 0.27 (sugars) to 0.70 (lactose) for men and from 0.37 (sugars) to 0.69 (lactose) for women. On average, 73 % of the subjects were categorised into the same or adjacent distribution quintile based on the two methods. In general, the FFQ overestimated the intakes compared with FR. Especially in women, FFQ validity for some nutrients was associated with the level of intake, subjects' age and, to a lesser extent, education but not BMI. In conclusion, the FFQ appears to be reasonably valid in the assessment of carbohydrate exposure variables, but the findings show a need for adjustment of diet-disease relationships for subjects' age and education.

Low-, medium- and high-glycaemic index carbohydrates and risk of type 2 diabetes in men.

Findings on dietary glycaemic index (GI) and glycaemic load (GL) as risk factors for type 2 diabetes have been controversial. We examined the associations of dietary GI and GL and the associations of substitution of lower-GI carbohydrates for higher-GI carbohydrates with diabetes risk in a cohort of Finnish men. The cohort consisted of 25 943 male smokers aged 50-69 years. Diet was assessed, at baseline, using a validated diet history questionnaire. During a 12-year follow-up, 1098 incident diabetes cases were identified from a national register. Cox proportional hazard modelling was used to estimate the risk of diabetes, and multivariate nutrient density models were used to examine the effects of substitution of different carbohydrates. Dietary GI and GL were not associated with diabetes risk; multivariate relative risk (RR) for highest v. lowest quintile for GI was 0·87 (95 % CI 0·71, 1·07) and for GL 0·88 (95 % CI 0·65, 1·17). Substitution of medium-GI carbohydrates for high-GI carbohydrates was inversely associated with diabetes risk (multivariate RR for highest v. lowest quintile 0·75, 95 % CI 0·59, 0·96), but substitution of low-GI carbohydrates for medium- or high-GI carbohydrates was not associated with the risk. In conclusion, dietary GI and GL were not associated with diabetes risk, and substitutions of lower-GI carbohydrates for higher-GI carbohydrates were not consistently associated with a lower diabetes risk. The associations of dietary GI and GL with diabetes risk should be interpreted by considering nutritional correlates, as foods may have different properties that affect risk.

Glycaemic index database for the epidemiological Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study.

Interest in the dietary glycaemic index (GI) and glycaemic load (GL) as risk factors for chronic diseases has grown in recent years but findings have been controversial. We describe the compilation of the GI database for the cohort studies within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study and the main characteristics associating with diet GI and GL. The ATBC Study enrolled 29 133 male smokers aged 50-69 years who filled in a dietary history questionnaire upon study entry. The dietary data included 1097 foods, of which 195 foods with no or a negligible amount of available carbohydrates were assigned a GI of zero. Based on preset methodological criteria for published GI studies, the GI value of a similar food was available for 130 foods, and the GI of related food was assigned to 360 foods. The GI values of these foods served in the GI calculation of 412 composite foods. The median diet GI among the ATBC Study participants was 67.3 (interquartile range 64.8-70.0), and the median diet GL was 175 (interquartile range 158-192). The intakes of carbohydrates, protein and fat decreased, and the intake of fibre increased, with increasing GI. The GL showed a positive correlation with intakes of carbohydrates and dietary fibre and a negative correlation with intakes of protein and fat. The GI studies available that fulfilled the minimum methodological requirements cover a sufficient amount of foods to form a meaningful GI database for epidemiological study. This, however, requires the availability of GI values for relevant local carbohydrate-containing foods.

Mapping geographical variation in obesity in Finland.

BACKGROUND: The prevalence of obesity varies across countries. However, less is known about the geographical, within-country variation. This study investigated and visualized the geographical differences in general obesity defined by body mass index (BMI) and in abdominal obesity defined by waist circumference and waist-to-hip ratio (WHR) in Finland. SUBJECTS AND METHODS: Data for the study consisted of three large population surveys: Health 2000 Survey with a nationally representative sample together with the National FINRISK Study conducted in five areas in 1997 and six areas in 2002. Altogether, 17 816 men and women aged 30-64 years participated in the surveys. In each survey, subjects' weight, height and circumferences of waist and hip were measured. The geographical pattern of mean anthropometric values and obesity prevalence were studied applying a Bayesian hierarchical approach and Geographical Information Systems. RESULTS: Both in men and women, the prevalence of obesity (BMI >/= 30 kg m(-2)) varied little across geographical areas, but it was smaller in cities compared with other areas across the country. In men, the prevalence of abdominal obesity defined both by waist circumference and WHR was higher in western Finland compared with southern and northern Finland. Also in women, the prevalence of abdominal obesity was highest in western Finland, especially as defined by waist circumference. CONCLUSIONS: Geographical variation in BMI was different and less prominent than in waist circumference and WHR. Abdominal obesity was surprisingly high in western Finland, the area seldom investigated. Mapping obesity gives a useful tool for professionals working in the field of health promotion.

Methodologic considerations in the measurement of glycemic index: glycemic response to rye bread, oatmeal porridge, and mashed potato.

BACKGROUND: Methodologic choices affect measures of the glycemic index (GI). The effects on GI values of blood sampling site, reference food type, and the number of repeat tests have been insufficiently determined. OBJECTIVE: The objective was to study the effect of methodologic choices on GI values. Comparisons were made between venous and capillary blood sampling and between glucose and white bread as the reference food. The number of tests needed for the reference food was assessed. Rye bread, oatmeal porridge, and instant mashed potato were used as the test foods. DESIGN: Twelve healthy volunteers were served each test food once and both reference foods 3 times at 1-wk intervals in a random order after they had fasted overnight. Capillary and venous blood samples were drawn at intervals for 3 h after each study meal. RESULTS: GIs and their CVs based on capillary samples were lower than those based on venous samples. Two tests of glucose solution as the reference provided stable capillary GIs for the test foods. The capillary GIs did not differ significantly when white bread was used as the reference 1, 2, or 3 times, but the variation was lower when tests were performed 2 and 3 times. Capillary GIs with white bread as the reference were 1.3 times as high as those with glucose as the reference. The capillary GIs of rye bread, oatmeal porridge, and mashed potato were 77, 74, and 80, respectively, with glucose as the reference. CONCLUSIONS: Capillary blood sampling should be used in the measurement of GI, and reference tests with glucose or white bread should be performed at least twice.