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Identifying comorbidities in polymyalgia rheumatica/giant cell arteritis (PMR/GCA) is crucial for patients’ outcomes. The present study aimed to evaluate the impact of the inflammatory process and glucocorticoid treatment on aortic arterial stiffness and body composition in PMR/GCA. 77 patients with newly diagnosed PMR/GCA were treated with oral glucocorticoids and followed for 40 weeks. Aortic pulse wave velocity (PWV) was measured at baseline and during the follow-up period and compared to the results of temporal artery biopsy (TAB) and 18F-FDG PET/CT. Body composition was assessed by total body DXA at baseline and the end of the study. Of 77 patients (49 (63.6%) female, mean of age: (71.8 ± 8.0)), 64 (83.1%) had pure PMR, 10 (13.0%) concomitant PMR and GCA, and 3 (3.9%) pure GCA. Compared to baseline values, aortic PWV was initially decreased at week 16 (p = 0.010) and remained lower than baseline at week 28 (p = 0.002) and week 40 (p

Background: Polymyalgia rheumatica (PMR)/Giant cell arteritis (GCA), common inflammatory diseases, are associated with increased risk of aortic stiffness, possibly due to an inflammatory process.1,2 Objectives: To evaluate the effect of steroid treatment on aortic stiffness in patients with PMR/GCA. Methods: This is an ongoing 1-year prospective cohort study. 37 consecutive patients with newly diagnosed PMR/GCA were included. Aortic pulse wave velocity (PWV) and aortic augmentation index normalized to heart rate of 75 beats per minute (AIx@75) were measured at baseline and subsequently at 1st and 4th months of treatment initiation with oral prednisolone. Results: Of 37 patients, 3 pts. were excluded from the study because of lack of interest or a change in the initial diagnosis. Of all included pts. 61.8% were female and mean age was 71 (69-74) years. At diagnosis, 24 pts. presented with pure PMR symptoms, 2 pts. with pure cranial GCA, 8 pts.with concurrent PMR and GCA. The mean of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) at baseline were 62.3±22.9 and 46.4±43.7, respectively. AIx@75 was significantly decreased after 4 months of treatment initiation (from 26.1±11.6 to 19.5 ±11.5, p=0.016). Though aortic PWV was decreased after 4 months of treatment initiation (from 12.3±2.4 to 11.6±2.4), the results was not statistically significant (p=0.070). We did not find any significant changes at 1st month, nor in aortic PWV neither in AIx@75. Conclusion: Steroid treatment may improve arterial stiffness in PMR/GCA patients due to suppression of the inflammatory process. However this is a time consuming effect and may not be seen as early as the first month. References: [1] Emamifar A, et al. Polymyalgia rheumatica and giant cell arteritis-three challenges-consequences of the vasculitis process, osteoporosis, and malignancy: A prospective cohort study protocol. Medicine (Baltimore). 2017;96(26):e7297. [2] Schillaci G, et al. Aortic stiffness is increased in polymyalgia rheumatica and improves after steroid treatment. Ann Rheum Dis 2012;71:1151-6. Disclosure of Interests: None declared

Background Poor adherence to the osteoporosis prophylaxis medications has been reported before, which may result in treatment failure.1 However findings of previous studies are controversial.1,2 Objectives To investigate the role of nurse-led telephone follow-up to increase the level of adherence to osteoporosis prophylaxis medications in patients with newly diagnosed Polymyalgia Rheumatica/Giant Cell Arteritis (PMR/GCA). Methods This is an ongoing 1-year prospective cohort study. 37 consecutive steroid treated patients with newly diagnosed PMR/GCA were included. Patients were seen by the physicians at baseline, 1st and 4th month, where they were interviewed about their compliance towards osteoporosis prophylaxis medications, i.e. Calcium/Vitamin D supplements and Bisphosphonates (if Tscore ≤−1), using a standardized questionnaire. Patients were therefore categorized as 100%, 50-100%, Results 85.3% and 75.8% of the patients were completely adherent to their osteoporosis medications at 1st and 4th months of treatment initiation, respectively. (figure 1) The difference between level of adherence to the osteoporosis medications at 1st (=week 4) and 4th month (=week 16) was not statistically significant. (P value:0.369). Decreased adherence in the patients was mainly due to forgetfulness. Conclusion Compared to the earlier findings we found a higher level of adherence in this group of patients. Nurse-led telephone follow up as well as educating the patients respecting the importance of the osteoporosis medications for preventing steroid related side effects, may enhance and subsequently maintain high level of adherence to the osteoporosis medications. Our findings are in line with our earlier study indicating a high level of adherence to the osteoporosis medications in PMR/GCA patients.2 References [1] Rossini M, et al. Determinants of adherence to osteoporosis treatment in clinical practice. Osteoporos Int. 2006;17:914-21. [2] Emamifar A, et al. Level of Adherence to Prophylactic Osteoporosis Medication amongst Patients with Polymyalgia Rheumatica and Giant Cell Arteritis: A Cross-Sectional Study. International Journal of Rheumatology. 2015;2015:783709. Disclosure of Interests None declared

Background We investigated the concordance between glucose effectiveness (SG) and insulin sensitivity (SI), derived from the unmodified dynamic non-insulin-assisted intravenous glucose tolerance test (IVGTT) implemented by SGMM and SIMM; simulation analysis and modelling/conversational interaction (SAAM/CONSAM) versus the eu/hyperglycaemic basal insulinaemic and the euglycaemic hyperinsulinaemic clamp (SGCLAMP and SICLAMP). Methods Twenty-seven of 30 normoglycaemic subjects completed a (1) euglycaemic hyperinsulinaemic clamp, (2) 6-h eu/hyperglycaemic near-normoinsulinaemic pancreatic clamp with hyperglycaemia present over the final 2 h of the clamp (Day 2 study), (3) identical clamp to (2) but with euglycaemia maintained over the entire 6 h (Day 3 study) and (4) IVGTT. SGCLAMP was calculated in two ways based on data from study (2) alone (Day 2 SGCLAMP210–240′) or from data from study day (2) and (3) (Day 2–3 SGCLAMP330–360′). Results SGMM was unrelated to the magnitude of endogenous insulin release (AIR). The single-day (Day 2) and two-day (Day 2 and 3) SGCLAMP protocols correlated (r = 0.72, p = 0.003), but SGCLAMP210–240′ was significantly (p = 0.001) higher than SGCLAMP330–360′. Employing the Day 2 and 3 SGCLAMP protocol, the whole body SGCLAMP330–360′ was similar to SGMM (1.80 ± 0.82 versus 1.73 ± 0.58 dL/min) and correlated (r = 0.45, p < 0.02). SGCLAMP210–240′ did not correlate with SGMM (r = 0.24). SIMM and SICLAMP were similar (0.093 ± 0.060 versus 0.087 ± 0.029 dL/min per mU/L) and correlated (r = 0.76, p < 0.001). Conclusions The time-dependent increase in glucose disposal observed during a prolonged 6-h clamp significantly influences the estimation of SGCLAMP, and significant concordance coefficients are observed between SGMM, and SGCLAMP330–360′, and SIMM and SICLAMP. Copyright © 2010 John Wiley & Sons, Ltd.

BACKGROUND: Insulin resistance was found in some but not in all previous studies of non-diabetic first degree relatives of Type 2 diabetic patients. Small study groups, ethnic differences and/or non-optimal techniques may explain the conflicting results. AIM: To study the impact of a family history of Type 2 diabetes on insulin action in a large group of non-diabetic Europeans using the 'gold standard' euglycaemic hyperinsulinaemic clamp technique. METHODS: Non-diabetic subjects (n = 235) with a positive family history of Type 2 diabetes (FH+) and 564 subjects with no family history of diabetes (FH-) were recruited from The European Group of Insulin Resistance (EGIR) database. This database includes measurements of insulin action using the insulin clamp technique (1 mU/kg per min) in normal glucose-tolerant individuals from 20 different European centres. In a subset of subjects the measurements were performed in combination with indirect calorimetry (n = 80 vs. 213 with and without family history of Type 2 diabetes). RESULTS: The body mass index (BMI) was slightly higher in FH+ compared with FH- (26.7 +/- 4.6 vs. 25.1 +/- 4.7 kg/m(2); P < 0.02). After correction for covariates according to differences between investigators and subject characteristics including BMI (multiple regression analysis), insulin-stimulated glucose disposal was lower in FH+ compared with FH- (P < 0.00001). Insulin-stimulated glucose oxidation was slightly increased in FH+ compared with FH-, and insulin-stimulated non-oxidative glucose metabolism was consequently markedly reduced in FH+ compared with FH- (P < 0.0005). CONCLUSION: Insulin resistance is present in European non-diabetic relatives of Type 2 diabetic patients. The insulin resistance is independent of degree of obesity and is restricted solely to the pathway of non-oxidative glucose metabolism. (Less)

Acute administration of the antilipolytic nicotinic acid analog acipimox to patients with noninsulin-dependent diabetes mellitus (NIDDM) is associated with increased peripheral and hepatic insulin sensitivity. However, long term acipimox treatment (250 mg, 3 times/24 h) of NIDDM patients does not improve blood glucose control, possibly due to rebound lipolysis. The current study assessed the influence of intensified acipimox administration (125 mg, 12 times/24 h) on diurnal plasma profiles of glucose, insulin, nonesterified FFA (NEFA), and triglycerides during a 3-day period. Eight NIDDM patients [mean age, 58.9 yr (range, 46-68); mean body mass index, 31.4 kg/m2 (range, 24.9-39.6)] were included in a randomized, double blind, placebo-controlled, cross-over study. Blood samples were collected every second hour during the study. The acipimox and placebo treatments were separated by a 2-week washout period. Acipimox treatment was associated with reduced diurnal mean plasma concentrations of NEFA [0.26 +/- 0.03 (+/- SEM) vs. 0.63 +/- 0.06 mmol/L; P < 0.001], triglycerides (1.74 +/- 0.21 vs. 2.10 +/- 0.18 mmol/L; P < 0.03), glucose (12.7 +/- 1.0 vs. 15.8 +/- 1.2 mmol/L; P < 0.002), and insulin (157 +/- 21 vs. 207 +/- 27 pmol/L; P < 0.05). However, despite the overall reduction in mean NEFA, during acipimox treatment NEFA increased from days 1-3 (0.18 +/- 0.03 vs. 0.34 +/- 0.04 mmol/L; P < 0.001), whereas plasma glucose (13.4 +/- 1.2 vs. 12.3 +/- 0.9 mmol/L; P < 0.03) and plasma insulin (168 +/- 23 vs. 148 +/- 17 pmol/L; P < 0.04) decreased steadily from days 1-3 during active treatment. In conclusion, inhibition of lipolysis using the intensified acipimox treatment regiment was associated with a pronounced blood glucose- and plasma insulin-lowering effect. However, minor rebound effects of lipolysis occurred in some patients despite the presence of allegedly effective acipimox levels. This suggests that caution should be employed concerning long term use of acipimox as a hypoglycemic agent in NIDDM patients.

With the aim of investigating glucose-mediated glucose disposal (glucose effectiveness [GE]) in 15 (3 female and 12 male subjects) insulin-resistant normoglycemic relatives of patients with type 2 diabetes (DM2), and 15 age-, sex-, and BMI-matched control subjects without a family history of DM2, we performed 2 studies: 1) a 5-h euglycemic near-normoinsulinemic pancreatic clamp with somatostatin (360 microg/h), insulin (0.25 mU x kg(-1) x min(-1)), glucagon (0.5 ng x kg(-1) x min(-1)), growth hormone (6 ng x kg(-1) x min(-1)), and tritiated glucose infusion and indirect calorimetry; and 2) on a separate day, an identical 5-h clamp but at hyperglycemia (approximately 12 mmol/l) over the last 2 h. Fasting plasma insulin (PI) concentrations were elevated in the relatives compared with control subjects (49 +/- 6 vs. 32 +/- 5 pmol/l, P < 0.04), whereas plasma glucose (PG) was not (5.6 +/- 0.1 vs. 5.5 +/-0.1 mmol/l). At the end (i.e., 4.5-5.0 h) of the euglycemic clamp (PG, 6.1 +/- 0.4 vs. 5.6 +/- 0.1 mmol/l; PI, 78 +/- 5 vs. 73 +/-6 pmol/l), peripheral glucose uptake (Rd(euglycemia)) was decreased in the relatives (2.93 +/- 0.08 vs. 3.70 +/-0.23 mg x min(-1) x kg(-1) fat free mass [FFM], P < 0.005), due to a decreased nonoxidative glucose disposal (0.83 +/-0.21 vs. 1.62 +/- 0.19 mg x min(-1) x kg(-1) FFM, P < 0.01), but hepatic glucose production (HGP) was increased (1.97 +/-0.19 vs. 1.50 +/- 0.13 mg x min(-1) x kg(-1) FFM, P < 0.05). At the matched end of the hyperglycemic clamp (PG, 12.7 +/-0.2 vs. 12.6 +/- 0.2 mmol/l; PI, 87 +/- 5 vs. 78 +/- 7 pmol/l), peripheral glucose disposal (Rd(hyperglycemia)) (5.52 +/- 0.22 vs. 5.92 +/- 0.29 mg x min(-1) x kg(-1) FFM, NS), nonoxidative glucose disposal (2.93 +/- 0.18 vs. 2.78 +/- 0.25 mg x min(-1) x kg(-1) FFM, NS), and HGP(hyperglycemia) (1.20 +/- 0.09 vs. 1.37 +/-0.23 mg x min(-1) x kg(-1) FFM, NS) were all identical. When the effectiveness of glucose itself on glucose uptake and production [(Rd(hyperglycemia) - Rd(euglycemia))/deltaPG and (HGP(euglycemia)- HGP(hyperglycemia))/deltaPG] was calculated, the relatives had a 22% increase in peripheral uptake (0.022 +/- 0.002 vs. 0.018 +/- 0.002 mg x min(-1) x kg(-1) FFM per mg/dl), due to a significantly increased nonoxidative glucose metabolism and enhanced suppression of HGP (0.0076 +/- 0.0021 vs. 0.0011 +/- 0.0022 mg x min(-1) x kg(-1) FFM per mg/dl, P < 0.05). In conclusion, in insulin-resistant relatives of DM2 patients, whole-body glucose-mediated glucose disposal is increased by GE enhancement of the muscle nonoxidative glucose pathway and by GE enhancement of the suppression of HGP. These mechanisms may represent a compensatory mechanism to the ongoing insulin resistance of these relatives.

OBJECTIVE: To evaluate the effect of clinically obtainable improvements in metabolic control in patients with type 1 diabetes on biochemical cardiovascular risk factors. RESEARCH DESIGN AND METHODS: Blood and 24-h urinary samples were obtained from 49 patients with type 1 diabetes before and after a run-in period and after 3 months of intervention, with frequent adjustment of insulin dosage according to measured blood glucose concentrations. RESULTS: The intervention caused a mean insulin dosage increment of 10%, a 20% decrease in fasting plasma glucose concentration, a 10% decrease in albumin corrected serum fructosamine, and a somewhat lesser decrease in HbAlc.A 14% decrease in the renal excretion of magnesium (Mg) was observed, but without a change in average serum Mg concentration. Serum HDL cholesterol increased 4%, and serum triglycerides decreased 10% as an average. Looking at individual patients, the decrease in serum triglycerides correlated with both the change in serum total Mg concentration and with the increase in insulin dosage. Using the change in serum total Mg concentration and in insulin dosage as independent variables in a multiple regression analysis, the coefficient of correlation with the decrease in serum triglycerides was 0.52. CONCLUSIONS: Moderate but clinically obtainable improvement of metabolic control in patients with type 1 diabetes seems to reduce the loss of Mg, increase serum HDL cholesterol, and decrease serum triglycerides. The decrease in serum triglycerides was associated with the change in serum total Mg concentration. These reductions in Mg loss and serum triglycerides might reduce the risk of developing cardiovascular disease in patients with type 1 diabetes.

Skeletal muscles in patients with non-insulin-dependent diabetes mellitus (NIDDM) are resistant to insulin; i.e., the effect of insulin on glucose disposal is reduced compared with the effect in control subjects. This defect has been found to be localized to the nonoxidative pathway of glucose disposal; hence, the deposition of glucose, as glycogen, is abnormally low. This defect may be inherited, because it is present in first-degree relatives to NIDDM patients two to three decades before they develop frank diabetes mellitus. The cellular defects responsible for the abnormal insulin action in NIDDM patients is reviewed in this article. The paper focuses mainly on convalent insulin signaling. Insulin is postulated to stimulate glucose storage by initiating a cascade of phosphorylation and dephosphorylation events, which results in dephosphorylation and hence activation of the enzyme glycogen synthase. Glycogen synthase is the key enzyme in regulation of glycogen synthesis in the skeletal muscles of humans. This enzyme is sensitive to insulin, but in NIDDM patients it has been shown to be completely resistant to insulin stimulation when measured at euglycemia. The enzyme seems to be locked in the glucose-6-phosphate (G-6-P)-dependent inactive D-form. This hypothesis is favored by the finding of reduced activity of the glycogen synthase phosphatase and increased activity of the respective kinase CAMP-dependent protein kinase. A reduced glycogen synthase activity has also been found in normoglycemic first-degree relatives of NIDDM patients, indicating that this abnormality precedes development of hyperglycemia in subjects prone to develop NIDDM. Therefore, this defect may be of primary genetic origin. However, it does not appear to be a defect in the enzyme itself, but rather a defect in the covalent activation of the enzyme system. Glycogen synthase is resistant to insulin but may be activated allosterically by G-6-P. This means that the defect in insulin activation can be compensated for by increased intracellular concentrations of G-6-P. In fact, we found that both hyperinsulinemia and hyperglycemia are able to increase the G-6-P level in skeletal muscles. Thus, insulin resistance in the nonoxidative pathway of glucose processing can be overcomed (compensated) by hyperinsulinemia and hyperglycemia. In conclusion, we hypothesize that insulin resistance in skeletal muscles may be a primary genetic defect preceding the diabetic state. The cellular abnormality responsible for that may be a reduced covalent insulin activation of the enzyme glycogen synthase. The compensation results in nearnormalization of glycogen synthesis, but the price diabetic subjects must pay to obtain this is hyperglycemia.

Background:Several chronic inflammatory diseases are associated with a higher risk of cancer.[1] Whether, this is the case in Polymyalgia Rheumatica (PMR) and Giant Cell Arteritis (GCA) is still a matter of debate.Objectives:To identify the prevalence of newly diagnosed cancers in patients with PMR and GCA by means of 18F-FDG PET/CT. Moreover, to compare the characteristics of the patients with and without cancer.Methods:Eighty consecutive patients with newly diagnosed PMR/GCA were studied. Diagnosis of PMR/GCA was confirmed by a 40-weeks follow up. A unilateral temporal artery biopsy (TAB) was also performed at the time of diagnosis. All included patients underwent an 18F-FDG PET/CT before, or in case of GCA, within 3 days of initiation of high dose oral glucocorticoid (40-75mg). All cancer-suspicious 18F-FDG-PET/CT findings were assessed thoroughly and malignant diseases were confirmed by histology. Total PMR and GCA scores were defined as the sum of a 4-point visual grading scale in each articular/periarticular site as well as arterial segment.Results:Of the 80 patients, 64 (83.1%) were diagnosed with pure PMR, 10 (13.0%) with concomitant GCA with PMR and 3 (3.9%) with pure GCA. Three patients were diagnosed with rheumatoid arthritis during follow up and excluded from the study. Five types of cancer in 4 (5.2%;95% CI:1.4-12.8%) patients were found. Two patients had breast cancer, one patient had adenocarcinoma of colon and one patient had adenocarcinoma of colon together with skin cancer. Besides, 4 (5.2%;95% CI:1.4-12.8%) patients had Monoclonal Gammopathy of Unknown Significance (MGUS). Age and C-reactive protein were significantly higher among those with solid cancers (p:0.049) and MGUS (p:0.017), respectively (Table1).Table 1.Characteristics of the patients with and without solid cancer ae well as MGUSVariablesCancer –,n=73Cancer +,n=4P-valueMGUS -, n =73MGUS +,n =4P-valueAge, mean±SD71.4±7.879.7±7.50.04971.9±8.070.2±9.20.79Gender, n(%)Female46(59.7%)3(3.9%)0.9947(61.0%)2(2.6%)0.62Constitutional symptoms, n(%)70(90.9%)4(5.2%)0.9970(90.9%)4(5.2%)0.99Shoulder girdle symptoms, n(%)68(88.3%)4(5.2%)0.9968(88.3%)4(5.2%)0.99Hip girdle symptoms, n(%)65(84.4%)3(3.9%)0.4064(83.1%)4(5.2%)0.99Cranial symptoms, n(%)19(24.7%)0(0%)0.5717(22.1%)2(2.6%)0.25Patients pain VAS75(50-85)62.5(50-75)0.5372.5(50 -80)87.5(77.5-95)0.07Patients global VAS80(60-90)62.5(50-75)0.3780(60-90)89.5(79.5-95)0.23Physician global VAS30(25-40)24.5(20-29)0.1530(22.5-40)37.5(32.5-45)0.17Erythrocyte sedimentation rate, mm[2-20]54(38-79)62.5(37.5-76)0.9354(38-77.5)57.5(39 -73.5)0.94C-reactive protein, mg/L[37(17-64)34(17.0-76)0.8033(17-60)98(68 -115)0.017TAB positive7(9.1%)0(0%)0.997(9.1%)0(0%)0.99Total PMR score14(10-17)12(5-15)0.3914(10-17)13(6-15.5)0.64Total GCA score0(0-0)0(0-0.5)0.890(0-0)0(0-0)0.34Clinical diagnosis, n(%)0.990.53 Pure PMR60(77.9%)4(5.2%)61(79.2%)3(3.9%) Pure GCA3(3.9%)0(0%)3(3.9%)0(0%) Concomitant PMR and GCA10(13.0%)0(0%)9(11.7%)1(1.3%)VAS: Visual analogue scaleConclusion:The prevalence of cancers in this cohort was higher, compared to the 1-year prevalence of all cancer sites of 1.2% among age-, gender- and region-matched background population in 2016. Occult malignancies are important and relatively prevalent findings in newly diagnosed PMR/GCA patients.References:[1]Hemminki K, et al. Cancer risk in hospitalized rheumatoid arthritis patients. Rheumatology (Oxford) 2008;47:698-701.Disclosure of Interests:None declared