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By Dr. Liji Thomas, MD Jul 25 2023 Reviewed by Danielle Ellis, B.Sc.

Type 2 diabetes melllitus (T2DM) is a common disease, the prevalence of which is increasing exponentially. It is estimated that by 2030, almost 440 million adults below the age of 80 will have diabetes. The consequences of T2DM on health and mortality have long been a focus of study. However, the medications used to control this dreaded disease have their effects on the body, causing specific adverse effects. Study: Diabetes medications and cancer risk associations: a systematic review and meta-analysis of evidence over the past 10 years. Image Credit: fizkes/Shutterstock.com

Cancer is found to occur at higher rates in people with diabetes, probably because both are associated with common risk factors. Diabetes drugs may also contribute to the risk of cancer.

In an attempt to discern the risk of cancer posed by certain diabetic drugs as well, the authors of a recent paper performed a systematic review and meta-analysis of all studies over the past ten years dealing with this topic. The research was published in Scientific Reports. Introduction

Cancer risk factors among people with diabetes include smoking, lack of physical exercise, overweight, and poor dietary quality. These reflect a state of inflammation, high blood sugar levels, and excessive amounts of insulin in the blood. Several studies have also shown that certain cancers occur more often among those who use specific diabetes drug categories.

The current review aimed to bring together the risk of multiple cancer types at various sites with the different types of medication used to treat diabetes. Earlier studies have looked mostly at how one class of medication affects cancer risk at different sites or, conversely, how all diabetes drugs affect cancer risk overall. The main focus remained on cancers of the breast, lung, liver, and pancreas, as well as CRCs.

The various drug classes explored were biguanides, those based on incretins, alpha-glucosidase inhibitors (AGIs), insulin secretagogues, thiazolidinediones, and insulins. What did the study show?

The review included 92 studies, of which three were randomized controlled trials (RCTs), while the majority (64) were cohort studies. The remaining comprised case-control studies. All three RCTs suffered from poor design, leading to a high risk of bias. Related StoriesUSC study reveals key details about how cancer cells metastasizeUnderstanding the impact of HPV on the vaginal microbiome and its role in cervical cancerWhat is the relative burden of oncologic and nononcologic mortality among long-term survivors of cancer in the US?

The cohort studies were mostly at low risk of bias, as were the case-control studies. The most studied cancers were CRCs and pancreatic cancers. Breast and lung cancers were mostly studied in cohort studies. Lung and liver cancers, and CRCs, were studied in both Asian and Western regions, whereas most research on breast, prostate, and pancreatic cancer was carried out in Western populations.

The results showed that colorectal cancer (CRC) and liver cancer occurred at lower rates among diabetic patients who used biguanides to control their blood sugar levels. The risk of liver cancer was reduced by an impressive 45% and that of CRC by 15%. In case-control studies alone, biguanide use was linked to an increase in pancreatic cancer odds by 25%.

Biguanides regulate energy and cellular metabolism, reducing the levels of oxidative stress, inflammation, and apoptosis, along with reduced body fat formation.

Similarly, breast cancer and liver cancer risk were reduced by about 15% with thiazolidinedione use, while the odds of lung cancer were lowered by 44%. These medications reduce the rates of breast cancer cell division and promote apoptosis while restricting neovascularization of tumors. In the liver, these agents cause the protein p27Kip1 to accumulate, limiting liver cell growth and, thus, perhaps, preventing cancerous changes.

Insulin use was linked to a 25% reduction in the odds of prostate cancer and a 10% drop in breast cancer odds. However, insulins were associated with massive increases in the risk of two cancers; pancreatic cancer risk went up by 240%, while there was a 74% increase in the risk of liver cancer.

The raised liver cancer risk was only among Western populations using insulin, with an increase of 250% in this subgroup. Insulin-resistant patients have high insulin levels in the portal circulation, which reaches the liver, and this might account for some of the risks.

Pancreatic cancers might form or grow faster when exposed to insulin, which promotes growth and cell division. However, severe diabetes is itself a risk factor of pancreatic cancer, adding a confounding factor to the etiology.

With insulin secretagogues, the risk of pancreatic cancer went up by 26%. Cohort studies, but not case-control series, showed a 20% rise in associated CRC following insulin secretagogue use. These agents promote insulin secretion by the pancreas, thus raising insulin-like growth factor 1 levels. Enhancing the rate of cell division may promote pancreatic cancer. What are the implications?

Overall, biguanide and thiazolidinedione use carried no risk, or potentially lower risk of some cancers, while insulin secretagogue and insulin use were associated with increased pancreatic cancer risk.”

The benefits of several medications used to treat diabetes extend to a reduction in the associated risk of cancer. At the same time, the risk of pancreatic and liver cancer shot up in association with the use of insulin and of pancreatic cancer with insulin secretagogues, though to a much lesser extent.

While showing associations between medication classes and cancer risk, the study also emphasizes regional differences as well as discrepancies between different study designs. Other confounding factors may have been at work, such as differences in nutritional status.

These findings suggest that it may be important to weigh the potential harms of insulin among patients with diabetes who are at high risk of liver or pancreatic cancers due to family history or other risk factors.” Journal reference: Chen, Y. et al. (2023) "Diabetes medications and cancer risk associations: a systematic review and meta-analysis of evidence over the past 10 years", Scientific Reports, 13(1). doi: 10.1038/s41598-023-38431-z. https://www.nature.com/articles/s41598-023-38431-z

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Sources: Rangers, Mets to swap Semien, Nimmo

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Sources: Rangers, Mets to swap Semien, Nimmo

The New York Mets and Texas Rangers have agreed to a trade that would send second baseman Marcus Semien to the Mets and outfielder Brandon Nimmo to the Rangers, sources told ESPN on Sunday.

Nimmo agreed to waive his no-trade clause, sources said, allowing the deal to be consummated, pending MLB approval. His tenure with the Mets started when they chose him with the 13th overall pick in the 2011 draft.

Semien, a three-time All-Star, joined the Rangers in 2022 and won a World Series with them the next season.

Texas entered the offseason looking for areas to save money, with its payroll being cut and four players — Semien, shortstop Corey Seager, and right-handers Jacob deGrom and Nathan Eovaldi — set to make in excess of $25 million next year. While the Rangers will actually take on more long-term money in Nimmo, who is owed $101.25 million over the next five seasons, the per-year sum is lower, with Semien set to make $72 million for the next three seasons.

The trade is the first move in what’s expected to be a busy winter for both teams — particularly the Mets. As a result of the team’s slow collapse over the season’s final 3½ months, New York missed the postseason and eventually underwent significant turnover in its coaching staff. The acquisition of Semien — who won a Gold Glove this year — aligns with president of baseball operations David Stearns’ primary goal this winter of improving run prevention.

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US hails ‘tremendous progress’ on Ukraine peace plan – but says negotiators ‘need more time’

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US hails 'tremendous progress' on Ukraine peace plan - but says negotiators 'need more time'

The US secretary of state has hailed a “tremendous amount of progress” on peace talks after the US and Ukraine delegations met in Geneva – but said that negotiators would “need more time”.

Marco Rubio said the meetings in Switzerland on Sunday have been “the most productive and meaningful” of the peace process so far.

He said the US was making “some changes” to the peace plan, seemingly based on Ukrainian suggestions, “in the hopes of further narrowing the differences and getting closer to something that both Ukraine and obviously the United States are very comfortable with”.

Mr Rubio struck an optimistic tone talking to the media after discussions but was light on the details, saying there was still work to be done.

US secretary of state Marco Rubio in Geneva after peace talks with Ukraine. Pic: Reuters
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US secretary of state Marco Rubio in Geneva after peace talks with Ukraine. Pic: Reuters

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Analysis: Rubio strikes an optimistic tone – but is light on detail

“I don’t want to declare victory or finality here. There’s still some work to be done, but we are much further ahead today at this time than we were when we began this morning and where we were a week ago for certain,” Mr Rubio said.

He also stressed: “We just need more time than what we have today. I honestly believe we’ll get there.”

Sky News’ defence analyst Michael Clarke said on the initial US-Russian 28-point peace plan that it was Donald Trump against the world, with maybe only Moscow on his side.

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Is Trump’s plan a ‘capitulation document’?

Mr Rubio praised the Ukrainian attitude towards the talks and said Mr Trump was “quite pleased” after he previously said in a social media post that Ukraine’s leaders had expressed “ZERO GRATITUDE” for US efforts.

Ukrainian President Volodymyr Zelenskyy said in his nightly address on Sunday that there are signs that “President Trump’s team hears us”.

In a news release on Sunday evening, the White House said the day “marked a significant step forward”.

“Ukrainian representatives stated that, based on the revisions and clarifications presented today, they believe the current draft reflects their national interests and provides credible and enforceable mechanisms to safeguard Ukraine’s security in both the near and long term,” it claimed.

Despite diplomatic progress in Geneva the finish line remains a long way off


John Sparks

John Sparks

International correspondent

@sparkomat

We’ve witnessed a day of determined and decidedly frantic diplomacy in this well-heeled city.

Camera crews were perched on street corners and long convoys of black vehicles swept down Geneva’s throughfares as the Ukrainians worked hard to keep the Americans on side.

Secretary of state Marco Rubio did not want to go into details at a press “gaggle” held at the US Mission this evening, but he seemed to think they had made more progress in the last 96 hours than the previous 10 months combined.

The Ukrainian leader Volodymyr Zelenskyy also seemed satisfied enough, posting on Telegram that there were “signals President Trump’s team is hearing us” after a day of “numerous meetings and negotiations”.

That said, we are a long way from the finish line here – something Rubio acknowledged when he said that any proposal agreed here would have to be handed over to the Russians.

At that point, negotiations to stop the war would surely get tougher.

President Putin has shown little or no inclination to stop the conflict thus far.

This, then, is the most important reason the Ukrainians seem determined to keep the Americans on side.

European leaders have presented a counter proposal to the widely criticised US-Russian peace plan, with suggestions including a cap on Ukraine’s peacetime army and readmitting Moscow into the G8.

This will only take place if the plan is agreed to by the US, Russia and Ukraine, and the G7 signs off on the move. Russia was expelled after annexing Crimea in 2014.

The counter proposal also includes US guarantees to Ukraine that mirror NATO’s Article 5 – the idea that “an armed attack against one NATO member shall be considered an attack against them all”.

The initial peace plan was worked up by the White House and Kremlin without Ukraine’s involvement, and it acquiesces to many of Russia’s previous demands.

Read more:
Who actually wrote US-Russian peace plan for Ukraine?
In full: Europe’s 28-point counter proposal to US-Russia plan

It covers a range of issues – from territorial concessions to reconstruction programmes, the future Ukrainian relationship with NATO and the EU, and educational reforms in both Ukraine and Russia.

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Technology

Google’s new AI model puts OpenAI, the great conundrum of this market, on shakier ground

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Google's new AI model puts OpenAI, the great conundrum of this market, on shakier ground

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