A review of Algerian medicinal plants used in the treatment of diabetes.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants are traditionally used in Algeria to treat many disorders, including diabetes mellitus. Knowledge of the plants that are used may provide insight on their properties, for further exploration. This study reviewed all the available published and unpublished reports concerning the use of herbal medicines in the treatment of diabetes in Algeria. AIM OF THE STUDY: To describe the plants used in Algeria to treat diabetes, as reported in the literature. MATERIAL AND METHODS: Systematic review of ethnobotanical papers published in the medical literature, from literature databases (Pubmed, Web of Science), as well as Google, for English, French and Arabic -language publication, and a manual search of local libraries and bookshops, as well as the university repository of PhD and master's theses. The reference lists of the papers retrieved were also examined for further papers. RESULTS: Many plants are cited in the ethnobotanical surveys, but only very few pharmacological studies were found. In the ethnobotanical surveys, 171 plants were reported, from 58 families of which the most often cited were Asteraceae, Lamiaceae and Apiaceae. The plants with the best evidence of use and activity are: Anabasis articulata (Forssk.) Moq., Trigonella foenum-graecum L., Centaurium erythraea Rafn, Artemisia herba-alba Asso, Marrubium vulgare L., Agathophora alopecuroides (Delile) Fenzl ex Bunge, Anabasis articulata (Forssk.) Moq., Hammada elegans (Bunge) Botsch., Helianthemum kahiricum Delile, Salsola baryosma (Schult.) Dandy, Salsola vermiculata L., Olea europaea L. CONCLUSION: Traditional herbal medicines are still very much used in Algeria to control diabetes. However they are generally poorly characterized and none have been properly tested in man. There is a need for systematic evaluation of the more commonly used plants to confirm their antidiabetic activity, identify possible mechanimss of action, and recommend best use.

Consumption of Alcopops During Brain Maturation Period: Higher Impact of Fructose Than Ethanol on Brain Metabolism.

Alcopops are flavored alcoholic beverages sweetened by sodas, known to contain fructose. These drinks have the goal of democratizing alcohol among young consumers (12-17 years old) and in the past few years have been considered as fashionable amongst teenagers. Adolescence, however, is a key period for brain maturation, occurring in the prefrontal cortex and limbic system until 21 years old. Therefore, this drinking behavior has become a public health concern. Despite the extensive literature concerning the respective impacts of either fructose or ethanol on brain, the effects following joint consumption of these substrates remains unknown. Our objective was to study the early brain modifications induced by a combined diet of high fructose (20%) and moderate amount of alcohol in young rats by 13C Nuclear Magnetic Resonance (NMR) spectroscopy. Wistar rats had isocaloric pair-fed diets containing fructose (HF, 20%), ethanol (Et, 0.5 g/day/kg) or both substrates at the same time (HFEt). After 6 weeks of diet, the rats were infused with 13C-glucose and brain perchloric acid extracts were analyzed by NMR spectroscopy (1H and 13C). Surprisingly, the most important modifications of brain metabolism were observed under fructose diet. Alterations, observed after only 6 weeks of diet, show that the brain is vulnerable at the metabolic level to fructose consumption during late-adolescence throughout adulthood in rats. The main result was an increase in oxidative metabolism compared to glycolysis, which may impact lactate levels in the brain and may, at least partially, explain memory impairment in teenagers consuming alcopops.

Progression of skin autofluorescence of AGEs over 4 years in patients with type 1 diabetes.

BACKGROUND: The deposit of advanced glycation end-products is involved in diabetic complications. It can be evaluated by measuring the skin autofluorescence (sAF). We searched whether sAF progressed over 4 years in type 1 diabetes and analysed its relationship with the development of nephropathy. METHODS: Two measurements of skin autofluorescence (sAF) were completed on 154 patients during years 2009 and 2013. Baseline factors associated with the progression of sAF were analysed by multivariate regression analysis. The relations among sAF progression, microalbuminuria, and impaired estimated glomerular filtration rate (eGFR) were analysed by logistic regression analysis. RESULTS: The patients were 51 ± 16 years old, with duration of diabetes of 23 ± 13 years, HbA1c: 7.7 ± 1.0%, 20.7% were treated by continuous subcutaneous insulin infusion (CSII). The sAF progressed by +18.1% over 4 years. Two interacting (P = .04) variables were associated with the later progression of sAF: mildly impaired eGFR and treatment by CSII. The patients with mildly impaired eGFR had the highest progression of sAF (+11.5% P = .01). Continuous subcutaneous insulin infusion was associated with a reduced progression of sAF in patients without kidney impairment (ß = -7.2%, P = .01). A +10% progression of sAF during the follow-up was associated with more microalbuminuria: OR = 1.45, P = .02, and more mildly impaired eGFR (<90 mL/min/1.73 m2 ): OR 1.22, P = .03 at 4 years of follow-up. CONCLUSIONS: The skin autofluorescence of advanced glycation end-products progresses in patients with type 1 diabetes, more if they have diabetic nephropathy, less if they are treated by continuous subcutaneous insulin infusion. This progression is associated with the development of nephropathy.

Nitrogen monoxide and carbon monoxide transfer interpretation: state of the art.

Just a few clinicians routinely measure the subcomponents of the lung diffusing capacity for Carbone monoxide (DLCO ). This is because the measurement of membrane and blood conductances for CO (DmCO and DbCO  = Î¸CO  × Vc , respectively) by the classic Roughton and Forster method is complicated and time consuming. In addition, it mistakenly assumes a close relationship between alveolar oxygen partial pressure (PAO2 ) and mean intracapillary oxygen partial pressure (PcapO2 ) which is the true determinant of specific conductance of haemoglobin for CO (θCO ). Besides that, the critical multistep oxygenation method along with different linear equations relating 1/θCO to PcapO2 gave highly scattered DmCO and Vc values. The Dm and Vc can also be derived from a simultaneous measurement of DLNO and DLCO with the blood resistance for NO assumed to be negligible. However, recent in vitro and in vivo experiments point towards a finite value of θNO (about 4·5 mlNO  × mlblood-1  × min-1  × mmHg-1 ). Putting together the arguments and our clinical data allows us to report here the state of the art in partitioning the CO diffusing capacity into its constitutive components, with the goal to encourage further studies examining the sensitivity of DmCO and Vc to alterations observed in parenchymal diseases.

Skin autofluorescence predicts cardio-renal outcome in type 1 diabetes: a longitudinal study.

BACKGROUND: We aimed to analyze the relationships between skin autofluorescence (SAF) and incident macrovascular events and renal impairment after 4 years of follow-up in patients with type 1 diabetes (T1D). METHODS: Two hundred and forty-three patients (51.2 ± 16.7 years old) with T1D participated. SAF was measured by AGE-Reader-TM at inclusion. Macrovascular events (MVE), estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (AER) were recorded then and 4 years later. Multivariate logistic regression was used to analyze the relationships between SAF and incident MVE and renal profile 4 years later. RESULTS: Patients with incident MVE had a higher SAF (p = 0.003). SAF predicted incident MVE after adjustment for age, sex, body mass index, tobacco, diabetes duration, hypertension, HbA1c, AER, eGFR (OR 4.84 [95 % CI 1.31-17.89], p = 0.018). However, this relation was no longer significant after adjustment for history of MVE. An inverse relation was found between SAF and incident eGFR (p = 0.0001). Patients with incident eGFR <60 ml/min/1.73 m(2) had a SAF higher than patients with normal eGFR. After adjustment for the previous criteria, SAF remained associated with the risk of impaired incident eGFR (OR 7.42 [95 % CI 1.59-34.65], p = 0.018). No relation was found between SAF and increased AER 4 years later. CONCLUSIONS: SAF predicts MVE in patients with T1D, adjusted for cardiovascular risk factors but the most powerful predictive factor remains history of MVE. SAF also predicts eGFR impairment, adjusted for initial AER and renal function. SAF could be a useful non-invasive tool for estimating risk of cardiovascular or renal impairment in patients with T1D.

Energy expenditure and nutritional complications of metabolic syndrome and rheumatoid cachexia in rheumatoid arthritis: an observational study using calorimetry and actimetry.

OBJECTIVE: Altered energy expenditure may contribute to the nutritional complications of RA, metabolic syndrome (MS) and rheumatoid cachexia (RC). The main aim of this study was to evaluate whether the altered resting energy expenditure (REE) and physical activity (PA)-related energy expenditure (EE) are related to the duration of RA and inflammatory activity and nutritional complications in RA. METHODS: Among patients with well-characterized RA (duration, activity: DAS28 ESR), we measured REE by indirect calorimetry, and PA-EE by actimetry (SenseWear Armband). MS was defined according to the International Diabetes Federation criteria and RC from DXA body composition analysis. The relations between the characteristics and nutritional complications, and EE were analysed by linear regression. RESULTS: Fifty-seven patients were included [73% women, age 57 (10) years] with a wide range of disease duration: 3.8 (3.0) years, and DAS28 ESR: 3.9 (1.4). The mean REE was 1486 (256) kcal/day, associated with the DAS28 ESR (ß = +0.21, P = 0.02 after adjusting for gender and fat free mass). The prevalence of MS and RC was, respectively, 24 and 18%, and they were unrelated to each other. The patients with MS and/or RC had double the longstanding RA score (P < 0.05), twice the homeostasis model assessment of insulin resistance values (P = 0.052) and halved levels of PA (P < 0.05 for metabolic equivalent tasks (METs) and number of steps/day). Two modifiable factors were associated with the presence of MS and/or RC: a low level of PA as METs [exp(B) = 0.03, P = 0.009] and the use of glucocorticoids [exp(B) = 4.08, P = 0.046]. CONCLUSION: Low levels of PA and treatment by glucocorticoids are associated with the nutritional complications of RA, suggesting the potential for therapeutic interventions.

Time-dependent effect of ethanol force-feeding on glycogen repletion: NMR evidence of a link with ATP turnover in rat liver.

The purpose was to study the hepatic effects of low-dose ethanol on the links between ATP and glycogen production. Fasted male Wistar rats received a single force-feeding of glucose plus ethanol or isocaloric glucose. At different times after force-feeding (0-10 h), glycogen repletion and ATP characteristics (content, apparent catalytic time constant, mitochondrial turnover) were monitored by (13)C- or (31)P-nuclear magnetic resonance (NMR) in perfused and isolated liver. In vivo glycogen repletion after force-feeding was slower after glucose plus ethanol vs. glucose (12.04 ± 0.68 and 8.50 ± 0.86 µmol/h/g liver wet weight [ww], respectively), reaching a maximum at the 6th hour. From the 3rd to the 8th hour, glycogen content was lower after glucose plus ethanol vs. glucose. After glucose plus ethanol, the correlation between glycogen and ATP contents presented two linear steps: before and after the 3rd hour (30 and 102 µmol glycogen/g ww per µmol ATP/g ww, respectively, the latter being near the single step measured in glucose). After glucose plus ethanol, ATP turnover remained stable for 2 h, was 3-fold higher from the 3rd hour to the 8th hour, and was higher than after glucose (2.59 ± 0.45 and 1.39 ± 0.19 µmol/min/g ww, respectively). In the 1st hour, glucose plus ethanol induced a transient acidosis and an increase in the phosphomonoesters signal. In conclusion, after ethanol consumption, a large part of the ATP production was diverted to redox re-equilibrium during the first 2 h, thereby reducing the glycogen synthesis. Thereafter, the maintenance of a large oxidative phosphorylation allowed the stimulation of glycogen synthesis requiring ATP.

Effect of Centaurium erythraea Rafn, Artemisia herba-alba Asso and Trigonella foenum-graecum L. on liver fat accumulation in C57BL/6J mice with high-fat diet-induced type 2 diabetes.

ETHNOPHARMACOLOGICAL RELEVANCE: Centaurium erythraea Rafn (CE), Artemisia herba-alba Asso (AHA) and Trigonella foenum-graecum L. (TFG) are traditionally used to treat type 2 diabetes in Algeria, previous studies have found that extracts of these plants were effective to treat or prevent experimental diabetes induced by high-fat diet (HFD). AIM OF THE STUDY: Describe the additional effects of these extracts on lipid tissue deposition in HFD. MATERIALS AND METHODS: Male C57BL/6J mice were fed with HFD to induce type 2 Diabetes. Groups of mice were given plant extracts orally at 2g/kg/bodyweight daily for 20 weeks during establishment of diabetes, or for 18 weeks after confirmation of diabetes at the 17th week. Liver and other tissue samples were stained with Oil Red O. RESULTS: Liver steatosis was confirmed with HFD. CE, AHA and TFG extracts improved liver steatosis by the end of the preventive (20 weeks) and curative periods (35 weeks). This was most marked for CE extract (p<0.05), less so with TFG and AHA. No steatosis was found in other tissues. CONCLUSION: CE extract had a clear hepatoprotective effect in this mouse model of diet-induced type 2 diabetes. AHA and TFG had a minimal or no significant effect on steatosis. Beyond its effect as an antidiabetic agent, CE may also be promising to prevent or treat non-alcoholic liver steatosis.

Autofluorescence of Skin Advanced Glycation End Products: Marker of Metabolic Memory in Elderly Population.

BACKGROUND: Advanced glycation end products are involved in the vascular complications of diabetes, in chronic kidney disease, and in the aging process. Their accumulation in the elderly people, as reflected by skin autofluorescence (sAF), may be a marker of metabolic memory. We aimed to examine the association of sAF with glycemic and renal status 10 years earlier in older persons. METHODS: In retrospective cohort study, 328 elderly community dwellers aged of 75 years and over had sAF measurement 10 years after their inclusion in the Three-City cohort. Fasting plasma glucose and serum creatinine were measured at baseline and at 10-year follow-up. In 125 participants, HbA1c was available at these two times. Associations between sAF and the glycemic and renal status 10 years before were analyzed by multivariate linear regression adjusted for age, sex, hypertension, body mass index, hypertriglyceridemia, and smoking. RESULTS: Participants were 82.4 (standard deviation = 4.1) years on average, and their mean sAF was 2.8 (standard deviation = 0.7) arbitrary units (AU). After adjustment, sAF was higher in participants with long-standing diabetes (+0.38 AU, p = .01) or chronic kidney disease (+0.29 AU, p = .02) compared with healthy participants. sAF was related to fasting plasma glucose (+1 mmol/L associated with +0.08 AU, p = .01) and HbA1c (+1% associated with +0.15 AU, p = .03) 10 years earlier, but not to the current fasting plasma glucose (p = .82) and HbA1c (p = .32). sAF was also related to the distal and current estimated glomerular filtration rates (p = .002 and .004, respectively). CONCLUSIONS: sAF reflects glycemic and renal status 10 years before, supporting its value as a marker of metabolic memory in the elderly people.

[A clinical approach to diagnosing diabetes]. / Le diagnostic de diabète, une démarche Clinique.

The diagnosis of diabetes does not exist as such. Diabetes is a biological symptom with diverse and numerous aetiologies. A high quality clinical approach comprises questioning and a clinical examination resulting in a diagnosis of type 1 or type 2 diabetes, or atypical diabetes. Subsequent treatment and therapeutic education are put in place depending on this diagnosis.The care pathway must therefore respect a certain order and approach in order to ensure its quality.

Resveratrol mainly stimulates the glycolytic ATP synthesis flux and not the mitochondrial one: a saturation transfer NMR study in perfused and isolated rat liver.

Our aim was to monitor the effects of resveratrol (RSV) on the respective contribution of glycolysis and oxidative phosphorylation on the unidirectional flux of ATP synthesis in whole isolated rat liver perfused with Krebs-Henseleit Buffer (KHB). The rate of tissular ATP supply was measured directly by monitoring the chemical exchange Pi toward ATP with saturation transfer (ST) (31)P nuclear magnetic resonance, a method applied for the first time for studying the effects of RSV. ST allows the measurement of the total cellular Pi→ATP chemical exchange; after specific inhibition of glycolysis with iodacetate, ST could provide the Pi→ATP flux issued from mitochondria. This latter was compared to mitochondrial ATP turn-over evaluated after chemical ischemia (CI), performed with specific inhibition (KCN) of oxidative phosphorylation, and measured by standard (31)P NMR spectroscopy. In controls (KHB alone), the apparent time constant (ks) of Pi exchange toward ATP as measured by ST was 0.48±0.04s(-1) leading to a total ATP synthesis rate of 37±3.9µmolmin(-1)g(-1). KHB+RSV perfusion increased ks (+52%; p=0.0009 vs. KHB) leading to an enhanced rate of total ATP synthesis (+52%; p=0.01 vs. KHB). When glycolysis was previously inhibited in KHB, both ks and ATP synthesis flux dramatically decreased (-87% and -86%, respectively, p<0.0001 vs. KHB without inhibition), evidencing a collapse of Pi-to-ATP exchange. However, glycolysis inhibition in KHB+RSV reduced to less extent ks (-41%, p=0.0005 vs. KHB+RSV without inhibition) and ATP synthesis flux (-18%). Using the CI method in KHB and KHB+RSV, KCN addition after glycolysis inhibition induced a rapid fall to zero of the ATP content. The mitochondrial ATP turnover R(t0) and its time constant kd mito were similar in KHB (1.18±0.19µmolmin(-1)g(-1) and 0.91±0.13min(-1)) and KHB+RSV (1.36±0.26µmolmin(-1)g(-1) and 0.77±0.18min(-1)). Since mitochondrial ATP turnover was not increased by RSV, the stimulation of Pi-to-ATP exchange by RSV mainly reflected an increase in glycolytic ATP synthesis flux. Moreover, the maintenance by RSV of a high level of Pi-to-ATP exchange after glycolysis inhibition evidenced a protective effect of the polyphenol, in agreement with our previous hypothesis of a stimulation of substrate flux throughout the glycolysis 3-carbon step.

Observation of the long-term effects of lifestyle intervention during balneotherapy in metabolic syndrome.

OBJECTIVE: Estimate the effect of lifestyle adjustment activities in patients with metabolic syndrome treated by prescribed balneotherapy. METHODS: Observational pilot cohort study with 12-month follow-up after multidimensional lifestyle training (physical, dietary, educational) during 3-week standard stay in the spa town of Eugénie-les-Bains. RESULTS: Of 145 eligible patients, 97 were included; 63 were followed and analysable. At inclusion all had ≥3 National cholesterol education program-Adult treatment panel III (NCEP-ATPIII) criteria defining metabolic syndrome, 76.2% were female, mean age was 61.2 years. At the end of follow-up (median:10.4 months, Inter-Quartile Range: [6.7;11.4]), 48 of these 63 patients (76.2%) no longer had metabolic syndrome (95%CI [65.7;86.7]). These 48 patients without metabolic syndrome at the end of follow-up represented 49.5% of the 97 included (95%CI [39.5;59.4]). CONCLUSIONS: Future studies of lifestyle interventions taking advantage of the spa environment can be expected to find least one third of patients free of metabolic syndrome at the end of 12-month follow-up in the intervention group.

Hepatic Steatosis, Carbohydrate Intake, and Food Quotient in Patients with NAFLD.

Is steatosis related to the spontaneous carbohydrate intake in patients with NAFLD? We performed dietary records for 24 patients with NAFLD, 3 months after their liver biopsy was performed and before the deliverance of a dietary advice. The food quotient, indicator of the proportion of calories from carbohydrates, was calculated as (1.00×% calories from carbohydrates/100) + (0.70×% calories from lipids/100) + (0.81×% calories from proteins/100). The associations between diet variables and steatosis% on the hepatic biopsies were tested by regression analysis, and diet variables were compared according to the presence of fibrosis. The subjects displayed a large range of steatosis, 50.5% ± 25.5 [10-90], correlated with their energy intake (1993 ± 597 kcal/d, r = 0.41, P < 0.05) and food quotient (0.85 ± 0.02, r = 0.42, P < 0.05), which remained significant with both variables by a multivariate regression analysis (r = 0.51, P < 0.05). For the 17/24 patients with a hepatic fibrosis, the energy intake was lower (fibrosis: 1863 ± 503 versus others: 2382 ± 733 kcal/d, P < 0.05), and their food quotients did not differ from patients without fibrosis. Hepatic steatosis was related to the energy and carbohydrate intakes in our patients; the role of dietary carbohydrates was detectable in the range of usual carbohydrate intake: 32% to 58% calories.

Can continuous glucose monitoring systems predict glycemia?

BACKGROUND: We investigated whether the arrow on a continuous glucose monitoring system (CGMS) screen predicts the course of the capillary glucose level 15 min later. SUBJECTS AND METHODS: Twenty-three patients with type 1 diabetes (age, 40±13 years; diabetes duration, 19±12 years; hemoglobin A1c, 8.5±1.5%) admitted for education in the use of a CGMS performed 242 observations: the arrow was noted at time 0, and the interstitial and capillary glucose levels were noted at time 0 and 15 min later. RESULTS: The capillary glucose courses were -15±28 mg/dL after a descending arrow (n=55), +1±23 mg/dL after a stable arrow (n=147) (P<0.001 vs. descending), and +2±23 mg/dL after an ascending arrow (n=40) (P<0.01 vs. descending), with similar findings for the 67 observations after an interstitial glucose level <100 mg/dL. There were 4.5% grossly erroneous arrows: six descending with later increasing and five ascending with later decreasing capillary glucose. CONCLUSIONS: Although there is a large room for improvement, the arrow on the CGMS screen does predict the decline in capillary glucose 15 min later.

Preventive and curative effect of Trigonella foenum-graecum L. seeds in C57BL/6J models of type 2 diabetes induced by high-fat diet.

ETHNOPHARMACOLOGICAL RELEVANCE: Trigonella foenum-graecum L. (TFG) is traditionally used to treat diabetes in North Africa. we therefore tested the effects of the hydro-alcoholic extract of TFG seeds in a C57/BL6J mouse model of diabetes induced by a standardised high-fat diet (HFD). MATERIALS AND METHODS: Plant extracts (2 g/kg daily) were administered orally by gavage at the start of HFD, or after confirmation of established diabetes (17th week), for 20 or 18 weeks, respectively, to male C57BL/6J mice. Animals were weighed; food intake and plasma glucose, lipid profile, insulin and insulin resistance were measured. RESULTS: TFG extracts opposed the development of diabetes: compared with untreated HFD mice, TFG-treated HFD mice had lower mean (± SD) plasma glucose (129.3 ± 39.4 vs. 183.1 ± 19.1mg/dL, p<0.05), plasma insulin (1.3 ± 0.8 vs. 3.1 ± 1.8 ng/mL, p<0.05) and triglycerides (18.9 ± 12.9 vs. 48.9 ± 12.1mg/dL, p<0.05), and less insulin resistance as estimated by the homeostasis model assessment (HOMA: 9.7 ± 11.1 vs. 38.3 ± 26.6, p<0.05). In mice with established diabetes, TFG reduced fasting plasma glucose (170.4 ± 24.1 vs. 229.0 ± 20.8 mg/dL, p<0.05), plasma insulin (1.7 ± 1.3 vs. 3.3 ± 14.3 ng/mL, p<0.05) and insulin resistance (HOMA: TFG: 19.2 ± 15.7 vs. HFD control: 38.5 ± 30.3, p<0.05). In addition, administration of TFG extract also caused significant reduction in triglycerides (17.9 ± 9.7 vs. 62.8 ± 18.3 mg/dL, p<0.05) and total cholesterol (1.30 ± 0.20 vs. 1.80 ± 1.10 g/L, p<0.05), and an increase in HDL-cholesterol (1.6 ± 0.2 vs. 1.2 ± 0.1 g/L). The plant extract had no effect on calorie intake or body weight. CONCLUSION: TFG extract opposed the development of experimental HFD diabetes in mice, and had an anti-diabetic effect in mice with established diabetes.

Fatigue symptoms relate to systemic inflammation in patients with type 2 diabetes.

Fatigue is frequent in patients with diabetes and this symptom appears to be more prominent in type 2 rather than type 1 diabetic subjects. Chronic inflammation represents one characteristic of type 2 diabetes that may contribute to fatigue symptoms. This possibility was assessed in a sample of 20 type 2 diabetic patients relatively to a group of 20 type 1 diabetic subjects. Specific dimensions of fatigue, including general fatigue, physical fatigue, reduced activity, mental fatigue and reduced motivation, were assessed using the Multidimensional-Fatigue-Inventory (MFI). Biological assays comprised the measurement of serum inflammatory markers [high-sensitive C-reactive-protein (hsCRP), high-sensitive interleukin-6 (hsIL-6), high-sensitive tumor-necrosis-factor-α (hsTNF-α) and neopterin]. Clinical parameters including indexes of adiposity were collected. In comparison to type 1 diabetic subjects, patients with type 2 diabetes exhibited higher fatigue scores, notably in the dimensions of general fatigue, physical fatigue and reduced activity, together with greater levels of inflammatory markers that correlated with indexes of adiposity. Regression analyses controlling for diabetes duration, insulin treatment status, glycemic control and fasting status, indicated that levels of inflammatory markers, in particular hsIL-6, hsCRP and neopterin, were associated with MFI fatigue dimensions in type 2 diabetic patients. Mediation analyses revealed that adiposity did not significantly account for the relationship of inflammatory markers with fatigue scores albeit coefficient regressions decreased somewhat when this variable was controlled for in regression models. These findings indicate that systemic low-grade inflammation relates to fatigue symptoms in patients with type 2 diabetes and suggest the involvement of inflammatory processes in the pathophysiology of diabetes-related fatigue.

Fatigue and cognitive symptoms in patients with diabetes: relationship with disease phenotype and insulin treatment.

Neurobehavioral symptoms are frequently reported in patients with diabetes. Nevertheless, the characterization of the specific symptom dimensions that develop in diabetic patients with respect to disease phenotype and treatment status remains obscure. This study comparatively assessed fatigue symptoms and cognitive performance using a dimensional approach in 21 patients with insulin-treated type 1 diabetes, 24 type 2 diabetic patients either insulin-free or undergoing insulin treatment for at least six months, and 15 healthy subjects. Specific dimensions of fatigue were assessed using the Multidimensional-Fatigue-Inventory (MFI). Cognitive performance on tests of choice reaction time, pattern recognition memory and spatial planning was evaluated using the Cambridge-Neuropsychological-Automated-Battery (CANTAB). Body mass index (BMI) and glycated-hemoglobin (HbA1C) concentrations were collected, as well as information on diabetes complications and disease duration. Patients with type 2 diabetes, regardless of insulin treatment status, exhibited higher scores of fatigue, primarily in the dimensions of general and physical fatigue as well as reduced activity. Cognitive alterations, in the form of longer reaction times and impaired spatial planning, were also detected in type 2 diabetic patients treated with insulin. These alterations were overall unrelated to glucose control, as reflected in HbA1C levels, and were not explained by complications and duration of diabetes. No specific alteration was measured in type 1 diabetic patients who exhibited fatigue scores and cognitive performance comparable to healthy participants. While associated with fatigue, increased BMI did not significantly account for the relationship of type 2 diabetes with general fatigue and physical fatigue. BMI, however, modulated the association of type 2 diabetes with reduced activity and the association of insulin-treated type 2 diabetes with psychomotor slowing. These findings reveal specific fatigue and cognitive symptoms in patients with type 2 diabetes and suggest the involvement of differential pathophysiological processes.