examined the innate immune pathway in AbdSc AT from lean, obese, and T2DM subjects, and 4) examined the association of circulating LPS in T2DM subjects. The findings showed that LPS increased TLR-2 protein expression twofold (P Ͻ 0.05). Treatment of AbdSc adipocytes with LPS caused a significant increase in TNF-␣ and IL-6 secretion (IL-6, Control: 2.7 Ϯ 0.5 vs. LPS: 4.8 Ϯ 0.3 ng/ml; P Ͻ 0.001; TNF-␣, Control: 1.0 Ϯ 0.83 vs. LPS: 32.8 Ϯ 6.23 pg/ml; P Ͻ 0.001). NF-B inhibitor reduced IL-6 in AbdSc adipocytes (Control: 2.7 Ϯ 0.5 vs. NF-B inhibitor: 2.1 Ϯ 0.4 ng/ml; P Ͻ 0.001). AbdSc AT protein expression for TLR-2, MyD88, TRAF6, and NF-B was increased in T2DM patients (P Ͻ 0.05), and TLR-2, TRAF-6, and NF-B were increased in LPStreated adipocytes (P Ͻ 0.05). Circulating LPS was 76% higher in T2DM subjects compared with matched controls. LPS correlated with insulin in controls (r ϭ 0.678, P Ͻ 0.0001). Rosiglitazone (RSG) significantly reduced both fasting serum insulin levels (reduced by 51%, P ϭ 0.0395) and serum LPS (reduced by 35%, P ϭ 0.0139) in a subgroup of previously untreated T2DM patients. In summary, our results suggest that T2DM is associated with increased endotoxemia, with AT able to initiate an innate immune response. Thus, increased adiposity may increase proinflammatory cytokines and therefore contribute to the pathogenic risk of T2DM.toll-like receptors; adipocytes; nuclear factor-B; inflammation; insulin OBESITY IS KNOWN TO REPRESENT one of the single most important risk factors for the increased risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease. In addition, an increase in central (visceral) adiposity confers higher metabolic risk. This increased metabolic risk is associated with subclinical inflammation, with several studies demonstrating increased levels of proinflammatory adipocytokines, such as IL-6 and TNF-␣ (32, 33), in patients with obesity and T2DM. Activation of proinflammatory adipocytokines in adipose tissue (AT) is coordinated through NF-B, a key transcription factor in the inflammatory cascade (2,10, 11,18,21,22,33,35,37,38). Adipocytes also secrete adiponectin (29,30,36,41,42), which has been shown to possess anti-inflammatory properties through its action on NF-B and is inversely correlated with obesity and diabetes (29,30,36,41,42). Evidence for the role of NF-B in AT has been shown in studies overexpressing the NF-B activator IKK␤ in mice, which resulted in increased inflammatory cytokine production and the onset of diabetes (7). In contrast, hepatocyte IKK␤ knockout (KO) mice demonstrated a decrease in circulating proinflammatory cytokines (3). This indicates that IKK␤ KO mice do not develop hepatic insulin resistance and glucose intolerance compared with their high-fat diet-fed counterparts. Further studies also illustrate that an inflammatory reaction, induced by the bacterial endotoxin lipopolysaccharide (LPS), is markedly attenuated in the IKK␤ KO mice (3

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ObjectiveTo determine the effectiveness of a theoretically based and individually tailored, text message based, diabetes self management support intervention (SMS4BG) in adults with poorly controlled diabetes.DesignNine month, two arm, parallel randomised controlled trial.SettingPrimary and secondary healthcare services in New Zealand.Participants366 participants aged 16 years and over with poorly controlled type 1 or type 2 diabetes (HbA1c ≥65 mmol/mol or 8%) randomised between June 2015 and November 2016 (n=183 intervention, n=183 control).InterventionsThe intervention group received a tailored package of text messages for up to nine months in addition to usual care. Text messages provided information, support, motivation, and reminders related to diabetes self management and lifestyle behaviours. The control group received usual care. Messages were delivered by a specifically designed automated content management system.Main outcome measuresPrimary outcome measure was change in glycaemic control (HbA1c) from baseline to nine months. Secondary outcomes included change in HbA1c at three and six months, and self efficacy, diabetes self care behaviours, diabetes distress, perceptions and beliefs about diabetes, health related quality of life, perceived support for diabetes management, and intervention engagement and satisfaction at nine months. Regression models adjusted for baseline outcome, health district category, diabetes type, and ethnicity.ResultsThe reduction in HbA1c at nine months was significantly greater in the intervention group (mean −8.85 mmol/mol (standard deviation 14.84)) than in the control group (−3.96 mmol/mol (17.02); adjusted mean difference −4.23 (95% confidence interval −7.30 to −1.15), P=0.007). Of 21 secondary outcomes, only four showed statistically significant improvements in favour of the intervention group at nine months. Significant improvements were seen for foot care behaviour (adjusted mean difference 0.85 (95% confidence interval 0.40 to 1.29), P<0.001), overall diabetes support (0.26 (0.03 to 0.50), P=0.03), health status on the EQ-5D visual analogue scale (4.38 (0.44 to 8.33), P=0.03), and perceptions of illness identity (−0.54 (−1.04 to −0.03), P=0.04). High levels of satisfaction with SMS4BG were found, with 161 (95%) of 169 participants reporting it to be useful, and 164 (97%) willing to recommend the programme to other people with diabetes.ConclusionA tailored, text message based, self management support programme resulted in modest improvements in glycaemic control in adults with poorly controlled diabetes. Although the clinical significance of these results is unclear, the findings support further investigation into the use of SMS4BG and other text message based support for this patient population.Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN12614001232628.

Diabetes is reaching epidemic proportions and with it carries the risk of complications. Disease of the foot is among one of the most feared complications of diabetes. The ultimate endpoint of diabetic foot disease is amputation, which is associated with significant morbidity and mortality, besides having immense social, psychological and financial consequences. As the majority of amputations are preceded by foot ulceration, it is crucial to identify those at an increased risk. Diabetic foot ulcers may develop as a result of neuropathy, ischaemia or both and when infection complicates a foot ulcer, the combination can become limb and life threatening. Structural abnormalities such as calluses, bunions, hammer toes, claw toes, flat foot and rocker bottom foot need to be identified and managed.