Men with type 1 diabetes osteoporosis risk › News in Science (ABC Science)
Sep 18, Men with type 1 diabetes are at an increased risk of developing osteoporosis, Study identifies diabetes, coeliac link, Science Online, 11 Dec In type 1 diabetes the body cannot produce insulin so people with this. May 10, Background and Objective: The incidence of diabetes mellitus is increasing. Male were more frequent with osteoporosis as compared to more the case of the relationship between type 2 diabetes and osteoporosis, there. The relationship between insulin resistance and osteoporosis in elderly male type 2 diabetes mellitus and diabetic nephropathyRapport entre la résistance à.
Type 2 diabetes - the most common form - normally develops later in life and can initially be maintained through healthy eating and exercise. A dynamic organ Hamilton and her team measured bone mineral density and bone turnover at the start of the study in and and then five years' later. Bone density is a measure of the strength of the bone, while measurements of bone turnover tracks the body's ability to form new bone and remove defective bone. Hamilton says many people did not realise that bone is an "incredibly dynamic organ" with cells constantly removing defective bone and forming new bone.
The current study shows type 1 diabetic men lost bone density "quite quickly" and at rates on a par with post-menopausal type 2 diabetic women. Hamilton says the reasons behind the impact on type 1 males remains unclear although the type 1 female participants remained pre-menopausal and increased their body mass index over the course of the study.
She says these factors may have offset the "deleterious effect" of diabetes on bone strength and may reflect that accelerated bone loss only becomes evident in type 1 women post-menopause. By contrast, over the course of the study those with type 2 diabetes had improved bone density after five years, with insulin acting as an anabolic to build up bone.
Despite this, Hamilton says type 2 diabetics still have a higher risk of breaking bones than the normal population. She says other longitudinal studies have shown no difference based on gender, however these studies were different in design.
The latter difference remained unaltered after further adjustment for duration of diabetes, but was slightly reduced when additionally adjusted for duration of insulin treatment and dose. This difference remained the same after adjustment for age. The percentages of both osteoporosis and osteopenia were higher in DM men when compared to both normal men and diabetic women.
There was no significant correlation between age-adjusted BMD values, and either diabetes duration, HBA1C values or age of onset of diabetes.The Importance of Calcium: Way Beyond the Bones - Dr. Eric Berg DC
In conclusion, this study showed low BMD values in type 1 DM men and showed the gender difference on the effect of diabetes on BMD where diabetic men had lower BMD values when compared with diabetic women.
Few studies have assessed bone markers in diabetic men. Despite the fact that there was not an increase in bone resorption markers in this study, this does not exclude a previous state of increased bone resorption. This is favored by the increase in OPG observed in this study that can be a protective mechanism of the skeleton to compensate for the possible previous increased bone resorption and bone loss. In another study, where more bone markers and hormonal markers, especially testosterone, were measured, Hamilton et al.
BMD values at forearm, spine, and hip were recorded. Only higher BMD at the spine was associated with diabetes duration. On multiple linear regression analysis, which adjusted for the natural logarithm Ln of the sex hormone-binding globulin concentration, smoking status, and alcohol consumption, it was shown that serum alkaline phosphatase was significantly negatively associated with BMD at 3 sites.
There was a positive association between Ln free testosterone and BMD at the forearm and a negative association between Ln osteocalcin and BMD at the forearm.
It was shown also that osteopenia was associated with low serum IGF-1 levels and bone formation markers. In the study that was mentioned previously, conducted by Krakauer et al. In another study [ 35 ], trying to follow type 1 DM patients over time, to study for the changes in bone density, 41 type 1 DM 19 female, 22 malesmean age 9 years, were followed for around 5 years.
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Two sites of the nondominant radius were analyzed by pQCT. It was shown in this study that at the 1st evaluation, mean SD value of trabecular BMD was even higher in type 1 diabetic patients than in controls, irrespective of age, sex, and Tanner stage. At the diaphysis, patients with type 1 DM had significantly reduced mean SD values for total, cortical, and medullary SCA as well as cortical BMD which had normalized at the 2nd measurement.
The younger the patients were at the disease manifestation and at the 1st evaluation, the more the increase in total CSA was detectable. As a conclusion, this study suggests a defect in bone accretion early in the course of type 1 DM, which then ameliorates with time.
A limitation of this study was the small number, but the strength is using pQCT as a tool for bone measurements and the 5-year followup.
Osteoporosis in Men with Diabetes Mellitus
Moreover, in another study [ 36 ] using both pQCT and DXA to measure bone mass and structure in 48 adolescents with type 1 DM 26 girls and 22 boyspQCT measurements were performed at the distal and shaft sites of the dominant radius and the right tibia. BMC, total cross-sectional area and trabecular density were determined for the distal sites, BMC, cortical density, and cortical cross-sectional area were determined for the shaft sites.
Type 1 and Type 2 DM Because most of the studies involved a small number of patients, in order to correct for this limitation and increase the power, a meta-analysis [ 30 ] including 80 papers on BMD and fracture risk in patients with type 1 and 2 DM was done and showed that in both genders there was an increased risk of fractures in both types of diabetes mellitus compared to non-diabetes mellitus.
Z-score in hip and spine was decreased in type 1 and increased in type 2 DM. In Conclusion The relationship between diabetes, both types, and osteoporosis seems complex. Mainly because the studies were limited by the small number, patients werenot followed up for a long period of time, studies were heteregenous with different diabetes control and duration, different complications, which makes it hard to draw a unique conclusion. More studies correcting for the mentioned limitations need to be performed.
Although the most popular one was the higher BMI in type 2 DM that can protect from osteoporosis, most of the studies discussed previously corrected for BMI, yet despite this correction there was still a higher BMD in patients with type 2 diabetes relatively to type 1 and healthy controls. Insulin and Insulin Growth Factors One popular hypothesis to the effect of diabetes on bone is through insulin, acting as a bone anabolic factor. The importance of this hypothesis is that it can also explain the pathophysiology behind the difference between type 1 and type 2 diabetic men.
Insulin seems to have both direct and indirect effects on bone. Support for a direct role of insulin in bone comes mainly from animal studies, specifically rats, where streptozocin-induced diabetes led to defects of bone mineralization. Moreover, rats lacking insulin receptors had impaired bone formation and low bone turnover [ 37 — 39 ].
In a recent study conducted by Fulzele et al. It was shown that osteoblasts lacking IR had severely impaired differentiation, with increased apoptosis. This led to a dramatic impairement in postnatal trabecular bone acquisition. Administration of IGF-1 did not correct for the abnormalities seen, showing the direct effect of insulin, independently of IGF-1 on the bone.
A high level of expression of insulin receptors on osteoblasts was reported [ 41 ], and insulin binding to these receptors led to cell proliferation, production of alkaline phosphatase, collagen synthesis, and glucose uptake [ 42 — 45 ]. The effect of insulin seems not only limited to osteoblasts, because in vitro studies showed that osteoclasts as well have insulin receptors where insulin can act to inhibit their action [ 46 ].
Human data support this hypothesis. A large study comprising of over subjects with type 1 diabetes mellitus showed lower IGF-1 levels as well as bone formation markers when compared to healthy controls [ 4748 ]. Moreover, low levels of IGF-1 were found to be associated with osteopenia in type 1 DM patients [ 48 ].
In contrast to type 1 diabetes mellitus where there is insulin deficiency, in type 2 diabetes mellitus there is insulin resistance and hyperinsulinemia which can explain the higher BMD in type 2 diabetes mellitus. Since the insulin resistance is selective and only restricted to the effect of insulin on glucose transport [ 49 ], the high insulin levels can still act on the osteoblast to increase BMD.
Indeed some investigators found a positive correlation between insulin levels and BMD [ 5051 ], yet others did not [ 5253 ]. In addition to a direct effect of insulin on osteoblast and osteoclast, insulin can indirectly act on the bone by decreasing sex-hormone binding globulin [ 54 — 57 ] leading to higher levels of free estrogen and testosterone, acting positively on the bone to increase BMD [ 58 ].
It can act indirectly by suppressing IGFBP-1 thus increasing the sensitivity of osteoblasts to IGF-1, then IGF-1 will modulate the actions of PTH on bone leading to a synergistic effect between insulin and PTH as well an indirect synergistic effect with other substances that mediate anabolic effects on bone [ 5960 ].
These are all theories, and more studies are needed to assess the effect of insulin on bone in male patients with diabetes. Diabetic Complications Uncontrolled diabetes with hyperglycemia has been suggested as a possible mechanism for osteoporosis in both type 1 and type 2. This can occur by the formation of nonenzymatic glycosylation of various bone proteins, including type 1 collagen, leading to impaired bone quality [ 61 ].
There are also some studies [ 62 ] associating high levels of pentosidine to higher risk of fractures in diabetic patients.
Is Osteoporosis a Common Complication in Type 2 Diabetes Patients?
Moreover, glucose is the principle source of energy for osteoclasts and is able to increase avian osteoclast activity in vitro in a dose-dependent manner [ 63 ]. Another indirect effect of hyperglycemia on bone can be through hypercalciuria secondary to glycosuria and other interactions with PTH and vitamin D metabolism [ 64 ].
Some studies have shown that type 2 diabetes mellitus is associated with lower vitamin D levels compared to healthy controls [ 6566 ]. Despite these theories, only some [ 67 ] but not all [ 3368 ] studies have demonstrated that glycemic control and HBA1C levels were associated with osteoporosis in diabetic patients.
Other than glycemic control, diabetic complications were incriminated in osteoporosis, mainly retinopathy [ 69 — 71 ] by decreasing exercise thus leading to decreased muscle mass and poor vision leading to increased incidence of falls, nephropathy [ 707273 ] by affecting bone metabolism, microangiopathy by directly affecting bone vascularisation, and neuropathy [ 74 ] by decreasing exercise.
Yet again other studies have shown contradictory results [ 2833 ] with no association between either complication and BMD. Bone Turnover and Bone Stiffness Most studies assessing bone turnover in diabetic patients were limited by the small number of patients included. In general, it was suggested that there is an imbalance between bone formation and bone resorption in diabetes.
The same was shown by Achemelal et al. Thus, it seems that in type 2 DM, there is a decreased bone formation. This was also shown by the study, previously mentioned above, by Krakauer et al.
Another contradictory study, done by Alexopulou et al. In contrast to bone formation, most studies [ 277576 ] have shown normal bone resorption markers in diabetic patients, suggesting with the associated low bone formation a state of low bone turnover or adynamic bone in diabetes. Again this is just a theory and more advanced studies are needed with more assessment of bone markers for both bone formation and resorption.
Hormonal Imbalance Since hypogonadism in men was associated with low BMD and fractures, and since most diabetic men have lower testosterone levels when compared to nondiabetics, it was suggested that diabetes can cause low BMD and higher risk of fractures through causing hypogonadism. Studies on this association are very limited, with one conducted by Asano et al. Conclusion Both osteoporosis and diabetes are increasing in men. Despite the fact that specific evidence-based recommendations based on the present data are not available and cannot be made, there must be awareness about the fact that diabetes, especially type 1, might be a risk factor for osteoporosis, that it is multifactorial, possibly affecting cortical and trabecular bone differently.
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Bone mass and strength in older men with type 2 diabetes: Effects of diabetes mellitus on bone mass in juvenile and adult onset diabetes. New England Journal of Medicine.
Decreased bone mineral density at the distal radius, but not at the lumbar spine or the femoral neck, in Japanese type 2 diabetic patients.