Aims/hypothesis. Although ischaemic heart disease is the predominant cause of mortality in older people with diabetes, age-specific mortality rates have not been published for patients with Type 1 diabetes. The Diabetes UK cohort, essentially one of patients with Type 1 diabetes, now has sufficient follow-up to report all heart disease, and specifically ischaemic heart disease, mortality rates by age. Methods. A cohort of 23,751 patients with insulintreated diabetes, diagnosed under the age of 30 years and from throughout the United Kingdom, was identified during the period 1972 to 1993 and followed for mortality until December 2000. Age-and sex-specific heart disease mortality rates and standardised mortality ratios were calculated. Results. There were 1437 deaths during the follow-up, 536 from cardiovascular disease, and of those, 369 from ischaemic heart disease. At all ages the ischaemic heart disease mortality rates in the cohort were higher than in the general population. Mortality rates within the cohort were similar for men and women under the age of 40. The standardised mortality ratios were higher in women than men at all ages, and in women were 44.8 (95%CI 20.5-85.0) at ages 20-29 and 41.6 (26.7-61.9) at ages 30-39. Conclusions/interpretation. The risk of mortality from ischaemic heart disease is exceptionally high in young adult women with Type 1 diabetes, with rates similar to those in men with Type 1 diabetes under the age of 40. These observations emphasise the need to identify and treat coronary risk factors in these young patients. [Diabetologia (2003) 46:760-765]

Deaths in patients with diabetes diagnosed under the age of 30 have been reported and comparisons drawn with mortality in the general population. To reduce these deaths attention must be paid both to the prevention of acute metabolic deaths and the early detection and treatment of cardiovascular disease and associated risk factors.

Raised risks of several cancers have been found in patients with type II diabetes, but there are few data on cancer risk in type I diabetes. We conducted a cohort study of 28 900 UK patients with insulin-treated diabetes followed for 520 517 person-years, and compared their cancer incidence and mortality with national expectations. To analyse by diabetes type, we examined risks separately in 23 834 patients diagnosed with diabetes under the age of 30 years, who will almost all have had type I diabetes, and 5066 patients diagnosed at ages 30 -49 years, who probably mainly had type II. Relative risks of cancer overall were close to unity, but ovarian cancer risk was highly significantly raised in patients with diabetes diagnosed under age 30 years (standardised incidence ratio (SIR) ¼ 2.14; 95% confidence interval (CI) 1.22 -3.48; standardised mortality ratio (SMR) ¼ 2.90; 95% CI 1.45-5.19), with greatest risks for those with diabetes diagnosed at ages 10 -19 years. Risks of cancer at other major sites were not substantially raised for type I patients. The excesses of obesity-and alcohol-related cancers in type II diabetes may be due to confounding rather than diabetes per se.

Abstract-Proliferation of vascular smooth muscle cells (VSMCs) contributes to intimal thickening during atherosclerosis and restenosis. The cadherins are transmembrane proteins, which form cell-cell contacts and may regulate VSMC proliferation. In this study, N-cadherin protein concentration was significantly reduced by stimulation of proliferation with fetal calf serum (FCS) and platelet-derived growth factor-BB (PDGF-BB) in human saphenous vein VSMCs. Furthermore, overexpression of a truncated N-cadherin, which acts as a dominant-negative increased VSMC proliferation. The amount of an extracellular fragment of N-cadherin (Ϸ90 kDa) in the media after 24 hours was increased by 12-fold by FCS and 11-fold by PDGF-BB, suggesting that N-cadherin levels are regulated by proteolytic shedding. Incubation with a synthetic metalloproteinase inhibitor or adenoviral overexpression of the endogenous tissue inhibitors of metalloproteinases (TIMPs) demonstrated that metalloproteinase activity was responsible in part for this proteolysis. Although total levels of ␤-catenin protein were not affected, ␤-catenin was translocated to the nucleus after stimulation with FCS and PDGF-BB. Our data indicates cadherin-mediated cell-cell contacts modulate proliferation in VSMCs. Furthermore, disruption of N-cadherin cell-cell contacts mediated in part by metalloproteinase activity occurs during VSMC proliferation, releasing ␤-catenin and possibly inducing ␤-catenin-mediated intracellular signaling. Key Words: smooth muscle Ⅲ proliferation Ⅲ cadherin Ⅲ metalloproteinase T he cadherins are a family of 30 transmembrane glycoproteins that are expressed by all cells that form solid tissues. The extracellular fragment of the cadherin protein binds to cadherin molecules on adjacent cells and permits homophilic cell-cell interactions. ␤-Catenin binds to the cytoplasmic region of the cadherin and regulates the formation of the cadherin/ catenin complex and its linkage to the actin cytoskeleton. In addition to serving a structural function by linking the actin cytoskeleton, ␤-catenin acts as signaling molecule that affects cell behavior, including cell proliferation, migration, differentiation, and cell survival. 1,2 ␤-Catenin can therefore be localized in the membrane-associated pool where it is required for cadherinmediated cell-cell adhesion and in the cytoplasmic/nuclear pool where it is involved in signaling in the Wnt/wingless growth factor signaling pathway. 3 Wnt target genes include cell cycle activators such as cyclin D1 and c-myc, and other genes including matrix-degrading metalloproteinases (MMPs) such as MMP-7, 4 MT1-MMP, 5 and fibronectin. 6 Furthermore, previous studies have shown that overexpression of cadherins and dominant-negative cadherins regulate proliferation of several cell types. [7][8][9][10] Proliferation of vascular smooth muscle cells (VSMCs) plays a key role in the development of pathological processes characterized by neointimal thickening, such as atherosclerosis, vascular rejection, and restenosis after angioplasty ...

Barriers to adherence to dietary therapies are numerous, but some, such as cost, and in the urban setting, communication with providers, are potentially remediable. Interventions aimed at improving patients' ability to modify their diet need to specifically address these areas. Furthermore, treatment guidelines need to consider patients' preferences and barriers when setting goals for treatment.