Study Design And Participants
Our study is a secondary analysis of a premix insulin study , which was conducted in the outpatient department of endocrinology of five hospitals in Jiangsu Province from October 2019 to April 2021. The study was approved by ethics committee of Nanjing First Hospital. All operations were in accordance with the ethical standards of the hospital and the 1964 Helsinki Declaration revised in 2013. All participants obtained informed consent.
The inclusion criteria were as follows: 1) patients aged > 18 years and diagnosed with T2DM according to World Health Organization 1999 diagnostic criteria of T2DM 2) patients using subcutaneous injection with premix insulin Bid/Tid, single drug and/or combination of oral hypoglycemic drugs, the treatment regimen was stable for more than 2 months 3) subjects were willing to undergo Flash Glucose Mornitoring examination
The exclusion criteria were as follows: 1) patients treated with GLP-1 agonist or systemic hormone therapy in recent 3 months 2) patients with insulin allergy or FGM intolerance 3) impaired liver and renal function, ALT 2.5 times higher than the upper limit of normal value serum creatinine was 1.3 times higher than the upper limit of normal 4) patients with acute metabolic diabetic complications, infection, stress or any other apparent condition as determined by the investigator .
The Changes Of Testosterone Levels Stratified By Glycated Albumin
To explore the influence of blood glucose changes on the testosterone level of patients, we subdivided the patients into four groups according to changes in GA: GA improved metformin group GA improved control group GA unimproved group GA unimproved control group . With 3-month treatment, the control-1 group had higher levels of TT, FT, and Bio-T than those at baseline . There was no statistically significant difference in TT, FT, and Bio-T levels among the other three groups before and after treatment . The change of TT level in the control group 1 was higher than that in the metformin group , and the change in the metformin group 2 was significantly lower than that in the control group 2 . As shown in Figures 3E, F, there was no difference between groups in the changes of FT and Bio-T.
Figure 3 TT, FT and Bio-T levels at baseline and endpoint in metformin and control groups under different stratification. the changes of TT, FT and Bio-T levels between metformin and control group before and after treatment under different stratification. 1=GA 0 2 =GA> 0 Data are mean ± SE.
Obesity And Low Testosterone
Obesity and low testosterone are tightly linked. Obese men are more likely to have low testosterone. Men with very low testosterone are also more likely to become obese.
Fat cells metabolize testosterone to estrogen, lowering testosterone levels. Also, obesity reduces levels of sex hormone binding globulin , a protein that carries testosterone in the blood. Less SHBG means less free testosterone.
Losing weight through exercise can increase testosterone levels.
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Address Any Underlying Medical Conditions
“I think something many men may not realize is that low testosterone is rarely a phenomenon on its own. It’s often linked to and potentially even caused by one or more underlying health condition that a man may not even know he has,” says Dr. Starke.
We’ve already discussed that obesity can contribute to low testosterone, but so can other common health conditions, including:
- Type 2 diabetes
- Metabolic syndrome
“Low testosterone can also be caused by medications you might be taking for a health condition you already know about or a previous therapy you’ve received, like chemotherapy and radiation,” adds Dr. Starke.
Seeing and being evaluated by a doctor who specializes in men’s health can help you understand what might be causing your low testosterone.
In addition, your doctor can help you understand which of the lifestyle changes above might be most important for you, recommend testosterone treatment and/or refer you to specialists who can help treat any underlying health condition that might be contributing to your low testosterone levels.
“If you’re having issues related to low testosterone, such as weight gain and difficulty exercising due to fatigue or muscle loss, starting testosterone treatment can make your weight loss goals and lifestyle improvements much easier to achieve,” adds Dr. Starke.
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Mechanisms Of Obesity Related Hpt Axis Dysregulation
Central mechanisms
In men with obesity related functional hypogonadism luteinising hormone is usually in the lower part of the normal range and inappropriate for the testosterone concentration. This indicates a central mechanism in the pathophysiology of obesity associated HPT axis dysregulation.
Leptin
Leptin is a cytokine hormone secreted by adipocytes in proportion the amount of fat stored and accordingly is a hormonal marker of energy sufficiency. Serum leptin concentration increases with obesity, but obesity is associated with resistance to the effects of leptin. Leptin is required for normal pulsatile secretory function of Gonadotrophin releasing hormone neurons in the arcuate nucleus of the hypothalamus . The permissive effects of leptin on GnRH pulsatility are mediated via kisspeptin expressing neurons in the ARC . In mice with diet induced obesity, serum testosterone and LH concentrations decrease, and the serum concentration of leptin increases, while the expression of leptin receptor, kisspeptin and the kisspeptin receptor GPR54, in hypothalamic neurons decreases .
Pro-inflammatory cytokines
Hypothalamic gliosis
Oestradiol
Circulating sex steroids inhibit LH and GnRH secretion by the pituitary and hypothalamus respectively.
Peripheral mechanisms
Effects on the testes.
Adipose tissue.
Sex hormone binding globulin variability.
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Testosterone Deficiency Diabetes And The Metabolic Syndrome
The association between low levels of testosterone and type 2 diabetes mellitus are well recognised, but it also appears that testosterone deficiency is common in men with diabetes regardless of type. Metabolic syndrome is a condition characterised by several co-occurring metabolic imbalances it often precedes type 2 diabetes mellitus, and is also associated with testosterone deficiency. There is considerable evidence that men with metabolic syndrome are more likely to develop hypogonadism and vice versa.
There is also a link between low testosterone levels and insulin resistance in men with type 1 diabetes. Testosterone replacement therapy has been shown to improve insulin metabolism.
Testosterone and testosterone metabolism
In men, testosterone is primarily produced by the Leydig cells of the testes. Testosterone production in the testes is stimulated when a mans pituitary gland produces a hormone called luteinising hormone . If either the pituitary gland or the testes are dysfunctional, testosterone production may decline or stop, leading to testosterone deficiency or hypogonadism.
| For more information, see Testosterone. |
Insulin and insulin metabolism
How does insulin resistance affect testosterone levels?
Evidence of the associations between diabetes, metabolic syndrome and testosterone deficiency
| For more information on TRT, see Testosterone Replacement Therapy. |
Randomisation And Drug Treatment
Patients were randomised to testosterone first or placebo first using a computer-generated random number. Treatment was with Sustanon 200 mg , a depot preparation of testosterone given by deep i.m. injection. Intramuscular injections were given once every 2 weeks, with patients receiving a total of six injections in each phase. The final assessment in each treatment phase was 1214 days after the previous injection. This regimen is commonly used as standard physiological testosterone replacement therapy in men with androgen deficiency and represents 3 months of testosterone treatment. Placebo was given as 0.9% normal saline. Drugs were drawn in identical syringes by a research nurse in a separate clinical room away from the patient and the doctor assessing the patient.
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Testosterone And Insulin Resistance
One of the clearest links between testosterone and diabetes is the relationship between low testosterone and insulin resistance.
When your body isnt responding normally to the insulin your pancreas produces, its referred to as insulin resistance.
To maintain normal blood sugar levels, your pancreas will work harder to produce more insulin. Over time, its hard to keep up with the demand. And this then leads to gradually increasing blood sugar levels, too.
Bit by bit, your blood sugar levels are rising until you suddenly learn at your routine check-up that your HbA1c is high enough to qualify as pre-diabetic which can later turn into type 2 diabetes.
You might also notice youre also gaining fat more easily and lose muscle mass more easily which just adds further to insulin resistance.
Muscle helps manage blood sugar levels and insulin resistance by burning more calories even when youre resting. The less testosterone you produce, the more muscle youll lose and the more calories youll store as body fat, which then increases insulin resistance and blood sugar levels.
Its a complicated system, and everything is affected! When your hormones are struggling, your blood sugar struggles. When your blood sugar struggles, your hormones struggle.
Testosterone Replacement Treatment Options
The question that remains is, does low testosterone cause or worsen medical problems like diabetes? Or are people who develop diabetes, or other health problems, simply more likely to also have low testosterone?
Studies to answer these questions are under way, but it will be years before we know the results. In the meantime, remember that testosterone replacement hasn’t been conclusively shown to improve any health condition other than testosterone deficiency and its symptoms. For men with low testosterone levels as measured by a blood test who also have symptoms of low testosterone, the decision to take testosterone replacement is one to make with your doctor.
Testosterone Replacement Therapy should only be used for men with low testosterone for erectile dysfunction/low libido. It is also indicated for transgender Female> Male assignments.
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Effect Of Weight Loss On Obesity Associated Functional Hypogonadism
In men with low serum testosterone attributable to obesity there is a linearly inverse association between decrease in weight and increase in serum testosterone concentration .
Diet induced weight loss.
Bariatric surgery.
Bariatric surgery produces substantial and durable weight loss with commensurate increases in serum testosterone SHBG, LH and FSH concentrations , and potentially sustained remission of T2D . The effects of bariatric surgery on serum testosterone are substantial. In aforementioned metanalysis bariatric surgery leading to a 32% reduction in body weight was associated with a 8.73 nmol/L increase in serum testosterone. Of note however whether increases in serum testosterone associated with weight loss are causal mediators of the improvement in androgen deficiency-like features observed in some obese men following weight loss remains unproven in one study that longitudinally followed obese men after bariatric surgery, the degree of weight loss, but the not the increase in serum testosterone was associated with improvements in sexual function .
Pharmacotherapy.
Effects Of Testosterone On Visceral Fat
Body fat is usually stored as subcutaneous fat or as visceral fat. Increased visceral fat increases the risk of developing diabetes or heart disease. In men, testosterone levels need to be adequate enough to maintain healthy fat distribution in the body. Conversely, men also need to maintain healthy body fat distribution to regulate this hormone. Visceral fat hampers testosterone production in the body. The excess abdominal fat further reduces testosterone production and increases that of estradiola female reproductive hormonein men. And this becomes a vicious cycle. Increased production of estradiol in men can lead to the development of added fat storage in different parts of the body. Some men develop Lack of sleep is one of the primary contributors to obesity, high blood glucose, low sex drive, inactivity, and sour moods.
6. Get some sun: Research has shown that Vitamin D may work as a natural testosterone booster. Soak up some sun in the early morning hours and add foods rich in Vitamin D, like mushrooms and fatty fish, to your diet.
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Sex Steroid Actions Beyond Circulating Testosterone
It is well recognized that relating a serum testosterone level to a clinical phenotype is an oversimplification, given that circulating testosterone levels, whether free or total , are unlikely to accurately reflect androgen action at the tissue level. Indeed, testosterone not only directly transactivates the AR but also acts via dihydrotestosterone and estradiol . DHT may mediate, at least in part, the metabolically favorable changes in body composition observed with testosterone therapy because, in a recent RCT of healthy men, DHT treatment significantly increased lean body mass and decreased fat mass, despite decreasing total testosterone to less than 5 nmol/liter . Furthermore, testosterone action is modulated by AR polymorphisms , as well as by transcriptional cofactors , likely in an age- and tissue-dependent fashion. Not surprisingly, therefore, circulating testosterone concentrations account for only 4067% of the variance in fat-free mass and muscle size . In addition, local androgen synthesis and inactivation may not be reflected in circulating testosterone levels .
Avoid Drugs And Alcohol Abuse
Abuse of drugs and alcohol has been linked to lower testosterone.
According to the National Institute of Alcohol Abuse and Alcoholism , alcohol use affects the glands and hormones involved in male reproductive health.
Further, alcohol can cause low testosterone levels due to the effects it has on the body, including causing hormonal reactions and cell damage.
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Can Testosterone Prevent Type 2 Diabetes In Men
Do you need more help?
This year heralds the outcomes of a 2-year Australian-led clinical trial to determine whether treatment with testosterone, added to a lifestyle-based weight management program, prevents T2D in men at high risk for the disease, or reverses it in those men newly diagnosed.
The testosterone for diabetes mellitus study, conducted across six sites in Australia is the the largest, and longest duration, testosterone clinical trial ever undertaken explains Professor Gary Wittert who is the Study Chair and Head of Medicine and Director of the Freemasons Foundation Centre for Mens Health at the University of Adelaide.
The prevalence of T2D is reaching epidemic proportions worldwide and in Australia is more common in men than women. The incidence of T2D in men increases markedly after the age of 50 and it is now the seventh leading cause of death in men1. Recent data show that in Australia 1 in 16, or about 780,000 adult men, have T2D2.
Type 2 diabetes occurs when the body is unable to control blood sugar levels and becomes insensitive to the hormone insulin.
What does testosterone have to do with this?
One of the complications of obesity, particularly when the excess fat accumulates around the abdominal area is a decrease in blood testosterone levels3. Studies have shown that low testosterone and obesity are strongly linked with an increased risk of T2D4.
Could testosterone therapy be the magic bullet?
Learn more
References
Is Testosterone Related To Diabetes
There are research showing that low level of testosterone and diabetes has relationship. Is it because of diabetes the testosterone level goes down or the other way round?
Testosterone plays in important role in fat storage Subcutaneous and Visceral
Subcutaneous means under the skin and visceral means around the abdominal area.
Low testosterone level has shown increase storage of fat near the abdominal area in men and high testosterone level in women has shown storage of fat around the abdomen which is one of the reason for diabetes or insulin insensitivity.
Low testosterone level is a reason for low libido and motivation, loss of muscle mass and could be diabetes.
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