Enhanced insulin action following subcutaneous co-administration of insulin and C-peptide in rats.

BACKGROUND: This study was undertaken to examine if C-peptide (C) may interact with hexameric insulin and facilitate its disaggregation into the physiologically active monomeric form. METHODS: Regular insulin (I) or an insulin analogue (IA) were injected s.c. in rats together with C or its C-terminal pentapeptide (PP). I or IA and C or PP were administered either as a physical mixture or into two separate s.c. depots. Whole body glucose utilization was evaluated using the euglycemic clamp technique. Phosphorylation of Akt/PKB and GSK in liver and skeletal muscles and 86Rb⁺ uptake by L6 cells were measured. RESULTS: S.c. injection of a mixture of I and C or I and PP resulted in a 30-55% greater (P < 0.01-0.001) and 15-27% (P < 0.05-0.001) longer stimulation of whole body glucose utilization than after separate injections. Insulin-stimulated phosphorylation of Akt/PKB in liver increased 35% more after injection of I and C in mixture compared with after separate injections. Phosphorylation of GSK3 was augmented by 50% (P < 0.05) following the injection of I and C in mixture compared with separate injections. Stimulation of myotubes with premixed I and C (1 nM) elicited 20% additional increase in ouabain-sensitive 86Rb⁺ uptake (P < 0.05) in comparison with the effect when I and C were added separately. CONCLUSIONS: Subcutaneous co-administration of insulin and C results in augmented insulin bioactivity at the level of tissue glucose uptake, intracellular signalling, and enzyme activation. These effects may be attributed to augmented C mediated disaggregation of hexameric insulin into its physiologically active monomeric form.

Rationalisation in public dental care--impact on clinical work tasks and mechanical exposure for dentists--a prospective study.

Swedish dentistry has been exposed to frequent rationalisation initiatives during the last half century. Previous research has shown that rationalisation often results in increased risk of developing work-related musculoskeletal disorders, thus reducing sustainability in the production system. In this prospective study, we assessed mechanical exposures among Swedish dentists in relation to specific rationalisations of clinical dental work during a six-year period. Body postures and movements of 12 dentists were assessed by inclinometry synchronised to video recordings of their work. No rationalisation effects could be shown in terms of a reduction in non-value-adding work ('waste'), and at job level, no major differences in mechanical exposure could be shown between baseline and follow-up. CONCLUSION: The present rationalisation measures in dentistry do not seem to result in rationalisation at job level, but may potentially be more successful at the overall dental system level. PRACTITIONER SUMMARY: In contrast to many previous investigations of the mechanical exposure implications of rationalisation, the present rationalisation measures did not increase the level of risk for dentists. It is highlighted that all occupations involved in the production system should be investigated to assess production system sustainability.

Working conditions, health and productivity among dentists in Swedish public dental care--a prospective study during a 5-year period of rationalisation.

In recent decades, comprehensive rationalisations have been implemented in public dentistry in Sweden. How rationalisations affect working conditions, health and production from a long-term perspective has been poorly investigated. This study aims to analyse changes and associations in dentists' working conditions, health and productivity during a 5-year period. In 2003 and 2008, 65 dentists responded to questionnaires measuring work conditions and health. Treatment times for patients and productivity were tracked in electronic registers. Paired t-tests showed that the number of treated adult patients per dentist increased, and perceived physical working conditions improved while perceived work control and leadership deteriorated. Structural equation modelling showed that physical factors were important for health and productivity. When assessing risks in the work environment, there is a need to understand the interaction of effects on working conditions and health due to rationalisations so as to increase the sustainability of production systems. PRACTITIONER SUMMARY: Dentistry in Sweden has undergone considerable change. Questionnaire surveys with dentists, undertaken in 2003 and 2008, found that the present rationalisations resulted in improved perceived physical working conditions. Aspects of the psychosocial working environment had deteriorated, however. This is a concern as health and workability are important for workplace efficiency.

Mechanical exposure among general practice dentists in Sweden and possible implications of rationalisation.

The present study investigates the dental work in terms of time distribution and mechanical exposure in value-adding work (VAW) and non-VAW. Further rationalisation of dental work would typically involve an increase in the proportion of VAW. Information on mechanical exposure within the classes of VAW and non-VAW may be used to predict possible implications of rationalisation. Sixteen dentists were investigated. Using a data logger, postures and movements were continuously recorded for each subject during the 4 h of work, which included the 45 min of video recording. Time distribution and mechanical exposure for the six different work activities identified were evaluated from the video recordings, using a loss analysis technique. VAW, which comprised 54% of the total working time, generally implied significantly more constrained mechanical exposures as compared with non-VAW. The results suggest that future rationalisation of dental work, involving a reduction of non-VAW, may increase the risk of developing musculoskeletal disorders. Statement of Relevance: The present study illustrates the potential effects of rationalisation on biomechanical exposures for dentists. The results highlight the significance of integrating ergonomic issues into the rationalisation process in dentistry in addition to ordinary workstation and tool design improvements performed by ergonomists.

Physical activity referrals in Swedish primary health care - prescriber and patient characteristics, reasons for prescriptions, and prescribed activities.

BACKGROUND: Over the past decade, practitioners in primary health care (PHC) settings in many countries have issued written prescriptions to patients to promote increased physical activity or exercise. The aim of this study is to describe and analyse a comprehensive physical activity referral (PAR) scheme implemented in a routine PHC setting in Ostergötland County. The study examines characteristics of the PARs recipients and referral practitioners, identifies reasons why practitioners opted to use PARs with their clients, and discusses prescribed activities and prescriptions in relation to PHC registries. METHODS: Prospective prescription data were obtained for 90% of the primary health care centres in Ostergötland County, Sweden, in 2004 and 2005. The study population consisted of patients who were issued PARs after they were deemed likely to benefit from increased physical activity, as assessed by PHC staff. RESULTS: During the two-year period, a total of 6,300 patients received PARs. Two-thirds of the patients were female and half of the patients were 45-64 years. Half of the patients (50.8%) who received PARs were recommended a home-based activity, such as walking. One third (33%) of the patients issued PARs were totally inactive, reporting no days of physical activity that lasted for 30 minutes, and 29% stated that they reached this level 1-2 days per week. The number of PARs prescribed per year in relation to the number of unique individuals that visited primary health care during one year was 1.4% in 2004 and 1.2% in 2005. Two-thirds of the combined prescriptions were issued by physicians (38%) and nurses (31%). Physiotherapists and behavioural scientists issued the highest relative number of prescriptions. The most common reasons for issuing PARs were musculoskeletal disorders (39.1%) and overweight (35.4%), followed by high blood pressure (23.3%) and diabetes (23.2%). CONCLUSION: Ostergötland County's PAR scheme reached a relatively high proportion of physically inactive people visiting local PHC centres for other health reasons. PAR-related statistics, including PAR-rates by individual PHC centres and PAR- rates per health professional category, show differences in prescribing activities, both by patient categories, and by prescribing professionals.

Protein dynamics in whole body and in splanchnic and leg tissues in type I diabetic patients.

To elucidate the mechanism of insulin's anticatabolic effect in humans, protein dynamics were evaluated in the whole-body, splanchnic, and leg tissues in six C-peptide-negative type I diabetic male patients in the insulin-deprived and insulin-treated states using two separate amino acid models (leucine and phenylalanine). L-(1-13C,15N)leucine, L-(ring-2H5)phenylalanine, and L-(ring-2H2) tyrosine were infused intravenously, and isotopic enrichments of [1-13C,15N]-leucine, (13C)leucine, (13C)ketoisocaproate, (2H5)phenylalanine, [2H4]tyrosine, (2H2)tyrosine, and 13CO2 were measured in arterial, hepatic vein, and femoral vein samples. Whole-body leucine flux, phenylalanine flux, and tyrosine flux were decreased (< 0.01) by insulin treatment, indicating an inhibition of protein breakdown. Moreover, insulin decreased (< 0.05) the rates of leucine oxidation and leucine transamination (P < 0.01), but the percent rate of ketoisocaproate oxidation was increased by insulin (P < 0.01). Insulin also reduced (< 0.01) whole-body protein synthesis estimated from both the leucine model (nonoxidative leucine disposal) and the phenylalanine model (disposal of phenylalanine not accounted by its conversion to tyrosine). Regional studies demonstrated that changes in whole body protein breakdown are accounted for by changes in both splanchnic and leg tissues. The changes in whole-body protein synthesis were not associated with changes in skeletal muscle (leg) protein synthesis but could be accounted for by the splanchnic region. We conclude that though insulin decreases whole-body protein breakdown in patients with type I diabetes by inhibition of protein breakdown in splanchnic and leg tissues, it selectively decreases protein synthesis in splanchnic tissues, which accounted for the observed decrease in whole-body protein synthesis. Insulin also augmented anabolism by decreasing leucine transamination.

Contributions of gluconeogenesis to glucose production in the fasted state.

Healthy subjects ingested 2H2O and after 14, 22, and 42 h of fasting the enrichments of deuterium in the hydrogens bound to carbons 2, 5, and 6 of blood glucose and in body water were determined. The hydrogens bound to the carbons were isolated in formaldehyde which was converted to hexamethylenetetramine for assay. Enrichment of the deuterium bound to carbon 5 of glucose to that in water or to carbon 2 directly equals the fraction of glucose formed by gluconeogenesis. The contribution of gluconeogenesis to glucose production was 47 +/- 49% after 14 h, 67 +/- 41% after 22 h, and 93 +/- 2% after 42 h of fasting. Glycerol's conversion to glucose is included in estimates using the enrichment at carbon 5, but not carbon 6. Equilibrations with water of the hydrogens bound to carbon 3 of pyruvate that become those bound to carbon 6 of glucose and of the hydrogen at carbon 2 of glucose produced via glycogenolysis are estimated from the enrichments to be approximately 80% complete. Thus, rates of gluconeogenesis can be determined without corrections required in other tracer methodologies. After an overnight fast gluconeogenesis accounts for approximately 50% and after 42 h of fasting for almost all of glucose production in healthy subjects.

Use of 2H2O for estimating rates of gluconeogenesis. Application to the fasted state.

A method is introduced for estimating the contribution of gluconeogenesis to glucose production. 2H2O is administered orally to achieve 0.5% deuterium enrichment in body water. Enrichments are determined in the hydrogens bound to carbons 2 and 6 of blood glucose and in urinary water. Enrichment at carbon 6 of glucose is assayed in hexamethylenetetramine, formed from formaldehyde produced by periodate oxidation of the glucose. Enrichment at carbon 2 is assayed in lactate formed by enzymatic transfer of the hydrogen from glucose via sorbitol to pyruvate. The fraction gluconeogenesis contributes to glucose production equals the ratio of the enrichment at carbon 6 to that at carbon 2 or in urinary water. Applying the method, the contribution of gluconeogenesis in healthy subjects was 23-42% after fasting 14 h, increasing to 59-84% after fasting 42 h. Enrichment at carbon 2 to that in urinary water was 1.12 +/- 0.13. Therefore, the assumption that hydrogen equilibrated during hexose-6-P isomerization was fulfilled. The 3H/14C ratio in glucose formed from [3-3H,3-14C]lactate given to healthy subjects was 0.1 to 0.2 of that in the lactate. Therefore equilibration during gluconeogenesis of the hydrogen bound to carbon 6 with that in body water was 80-90% complete, so that gluconeogenesis is underestimated by 10-20%. Glycerol's contribution to gluconeogenesis is not included in these estimates. The method is applicable to studies in humans of gluconeogenesis at safe doses of 2H2O.

Contributions by kidney and liver to glucose production in the postabsorptive state and after 60 h of fasting.

Contributions of renal glucose production to whole-body glucose turnover were determined in healthy individuals by using the arteriovenous balance technique across the kidneys and the splanchnic area combined with intravenous infusion of [U-13C6]glucose, [3-(3)H]glucose, or [6-(3)H]glucose. In the postabsorptive state, the rate of glucose appearance was 11.5 +/- 0.6 micromol x kg(-1) x min(-1). Hepatic glucose production, calculated as the sum of net glucose output (9.8 +/- 0.8 micromol x kg(-1) x min(-1)) and splanchnic glucose uptake (2.2 +/- 0.3 micromol x kg(-1) x min(-1)) accounted for the entire rate of glucose appearance. There was no net exchange of glucose across the kidney and no significant renal extraction of labeled glucose. The renal contribution to total glucose production calculated from the arterial, hepatic, and renal venous 13C-enrichments (glucose M+6) was 5 +/- 2%. In the 60-h fasted state, the rate of glucose appearance was 8.2 +/- 0.3 micromol x kg(-1) x min(-1). Hepatic glucose production, estimated as net splanchnic output (5.8 +/- 0.7 micromol x kg(-1) x min(-1)) plus splanchnic uptake (0.6 +/- 0.3 micromol x kg(-1) x min(-1)) accounted for 79% of the rate of glucose appearance. There was a significant net renal output of glucose (0.9 +/- 0.3 micromol x kg(-1) x min(-1)), but no significant extraction of labeled glucose across the kidney. The renal contribution to whole-body glucose turnover calculated from the 13C-enrichments was 24 +/- 3%. We concluded that 1) glucose production by the human kidney in the postabsorptive state, in contrast to recent reports, makes at most only a minor contribution (approximately 5%) to blood glucose homeostasis, but that 2) after 60-h of fasting, renal glucose production may account for 20-25% of whole-body glucose turnover.

Increasing stroke incidence in Sweden between 1989 and 2000 among persons aged 30 to 65 years: evidence from the Swedish Hospital Discharge Register.

BACKGROUND AND PURPOSE: Stroke mortality is decreasing in Sweden, as is the case in other Western European countries. However, both decreases and increases have been reported in Sweden for persons younger than age 65 years. The aim of this study was to compare the incidence of stroke in Sweden between the periods 1989 and 1991 and 1998 and 2000 in persons aged 30 to 65 years. METHODS: All first-ever stroke patients aged 30 to 65 years in the Swedish Hospital Discharge Register between 1989 and 2000 were included. RESULTS: The age-standardized, 3-year average incidence increased by 19%, from 98.9 to 118.0 per 100 000 among men, and by 33%, from 48.4 to 64.4 among women, between 1989 and 1991 and 1998 and 2000. The largest increase was seen among those younger than 60 years. On a county level, the change in age-standardized stroke incidence varied from small decreases (-3%) to large increases (82%). CONCLUSIONS: Stroke incidence increased in Sweden for both men and women between 1989 and 2000. The increase was larger among women. This calls for action when it comes to studying risk factors and planning for prevention and health promotion and indicates the need for gender-specific studies.